Thawing biological substances

ABSTRACT

Dry thawing systems and devices for thawing biological substances are provided herein. Methods for thawing biological substances are also provided.

CROSS-REFERENCE TO RELATED APPLICATIONS

The present application claims priority to U.S. Provisional ApplicationNo. 62/668,034, filed on May 7, 2018, and entitled “Device for Thawingof Biological Substances,” which is hereby incorporated by reference inits entirety.

FIELD

The present application relates to methods and devices for thawingbiological substances.

BACKGROUND

Bags containing biological substances such as plasma, blood, bloodproducts, and medication can be supplied to medical facilities fortransfusion in large volume on a daily basis. These bags can be frozen,stored in inventory upon arrival, and thawed to a designated temperaturejust prior to transfusion.

The quality of thawed biological substances can depend upon the processby which they are thawed. Underheating a biological substance can causepatients to experience hypothermia. Conversely, overheating a biologicalsubstance can cause severe damage (e.g., denaturation) to proteins andother components that can reduce the quality of the transfused fluid,endangering patients.

Accordingly, improved methods and devices are needed to thawingbiological substances.

SUMMARY

In general, methods and devices for thawing biological substances areprovided.

In one embodiment, a dry thawing device is provided and includes achamber frame configured to receive an enclosed biological substance,and a first heating assembly coupled to the chamber frame. The firstheating assembly has a heater configured to be in thermal communicationwith an enclosed biological substance that is received within thechamber frame. The device further includes an agitation device mountedwithin the chamber frame and configured to cause the first heatingassembly to pivot about a pivot axis relative to the chamber frame suchthat the first heating assembly can agitate an enclosed biologicalsubstance received within the chamber frame.

The device can have a variety of configurations. In one embodiment,first heating assembly can be linearly slidably movable relative to thechamber frame. The device can include at least one biasing element thatbiases the first heating assembly into contact with an enclosedbiological substance that is received within the chamber frame.

In other aspects, the device can include a chamber door that ispivotally coupled to the chamber frame and that is moveable between openand closed positions. A second heating assembly can be mounted on thechamber door. The second heating assembly can have a heater that, whenthe chamber door is in a closed position, is configured to be in thermalcommunication with an enclosed biological substance that is receivedwithin the chamber frame. The first heating assembly can be configuredto be positioned adjacent to a first side of an enclosed biologicalsubstance that is received within the chamber frame and the secondheating assembly can be configured to be positioned adjacent to a secondside of the enclosed biological substance that is opposite the firstside.

In other aspects, the device can include at least one temperature sensorconfigured to measure a temperature of at least one of the first heatingassembly and an enclosed biological substance received within thechamber frame. In another embodiment, the device can include a weightsensor configured to measure a weight of an enclosed biologicalsubstance that is received within the chamber frame. In another aspect,an overwrap bag can be disposed within the chamber frame, and theoverwrap bag can contain an enclosed biological substance.

In another embodiment, a dry thawing device is provided and includes achamber frame having a top portion, a bottom portion, and first andsecond opposed sidewalls coupled to the top and bottom portions. Asupport frame can be mounted to the bottom portion of the chamber frameand it can extend between the top and bottom portions of the chamberframe. An agitator plate can be pivotally coupled to the support frame,and the agitator plate can be configured to contact an enclosedbiological substance disposed within the chamber frame. An agitationdevice can be mounted to the support frame and it can be configured tocause pivotal motion of the agitator plate to thereby agitate anenclosed biological substance disposed within the chamber frame.

In one aspect, the agitation device can include a cam mechanismconfigured to cam the agitator plate to cause pivotal motion of theagitator plate. The agitator plate can extend between the top and bottomportions of the chamber frame and can be pivotally mounted at amid-portion thereof to the support frame.

In other aspects, the support frame can be slidably mounted to thebottom portion of the chamber frame. The support frame can be biasedtoward an enclosed biological substance disposed within the chamberframe to thereby bias the agitator plate toward an enclosed biologicalsubstance disposed within the chamber frame. The agitator plate caninclude a first heating assembly mounted thereon and configured toselectively generate thermal energy to heat an enclosed biologicalsubstance disposed within the chamber frame. In certain aspects, theagitator plate includes a top end and a bottom end, and pivotal motionof the agitator plate causes the top and bottom ends to move in oppositedirections.

The device can also include a chamber door mounted to the first end ofthe chamber frame. The chamber door can be moveable between open andclosed positions. When the chamber door is in the closed position, thechamber door and the agitator plate can define a cavity there betweenthat is configured to receive an enclosed biological substance. A secondheating assembly can be mounted on the chamber door, and the secondheating assembly can have a heater that is configured to selectivelygenerate heat to thaw an enclosed biological substance disposed withinthe cavity.

In another embodiment, a method for thawing a biological substance isprovided and includes positioning an enclosed biological substance in afrozen state within a cavity in a housing such that the enclosedbiological substance is in thermal communication with a first heatingassembly located within the housing, activating the heating assembly toheat and thereby thaw the enclosed biological substance, and activatingan agitation device to cause an agitator plate disposed within thehousing to pivot about a pivot axis and thereby agitate the enclosedbiological substance.

In certain aspects, the heating assembly can be mounted on the agitatorplate such that the heating assembly pivots within pivotal motion of theagitator plate. The agitation device can be activated while the heatingassembly is activated.

In one embodiment, a dry thawing device is provided and includes ahousing, a chamber frame disposed within the housing and having a baseextending from a first end to a second end, and a chamber door pivotallymounted to the first end of the base and disposed at a first end of thehousing. The chamber door can be movable between an open position, inwhich an enclosed biological substance can be inserted into a cavitywithin the housing, and a closed position, in which the chamber doorencloses the enclosed biological substance within the cavity. A firstheating assembly can be mounted on an inner surface of the chamber doorsuch that a heater of the first heating assembly is configured todeliver thermal energy to heat an enclosed biological substance disposedwithin the cavity.

The device can also include a second heating assembly disposed withinthe housing and having a heater that is configured to selectivelygenerate thermal energy to heat an enclosed biological substance that isreceived within the cavity. The first and second heating assemblies candefine the cavity for receiving the enclosed biological substance therebetween. The second heating assembly can be mounted on an agitator platedisposed within the housing and configured to pivot about a pivot axisto agitate an enclosed biological substance disposed within the cavity.The agitator plate can be pivotally mounted to a support plate that islinearly slidably mounted on the base of the chamber frame.

The device can also include at least one temperature sensor that isconfigured to measure a temperature of at least one of the first heatingassembly and an enclosed biological substance received within thecavity. The device can include a weight sensor that is configured tomeasure a weight of an enclosed biological substance that is receivedwithin the cavity. An overwrap bag can be disposed within the cavity andit can contain an enclosed biological substance.

In other aspects, the device can include a second chamber frame disposedwithin the housing and having a base extending from a first end to asecond end, and a second chamber door pivotally mounted to the first endof the base of the second chamber frame and disposed at a second end ofthe housing opposite to the first end. The second chamber door can bemovable between an open position, in which a second enclosed biologicalsubstance can be inserted into a second cavity within the housing, and aclosed position, in which the second chamber door encloses the secondenclosed biological substance within the cavity

In another embodiment, a dry thawing device is provided and includes ahousing having opposed top and bottom sides, opposed front and backsides extending between the top and bottom sides, and opposed left andright sides extending between the top and bottom sides and between thefront and back sides. A first chamber door is positioned on the leftside of the housing and is pivotally movable between open and closedpositions. The first chamber door has a first heating assembly mountedthereon and having a first heater that is configured to selectivelygenerate thermal energy to heat a first enclosed biological substancedisposed within the housing adjacent to the first chamber door. A secondchamber door is positioned on the right side of the housing and ispivotally movable between open and closed positions. The second chamberdoor has a second heating assembly mounted thereon and having a secondheater that is configured to selectively generate thermal energy to heata second enclosed biological substance disposed within the housingadjacent to the second chamber door.

In one aspect, a first agitator plate can be disposed within the housingto define a first cavity there between with the first chamber door such.The first cavity can be configured to receive a first enclosedbiological substance, and the first agitator plate can be configured topivot to agitate the first enclosed biological substance. A secondagitator plate can be disposed within the housing to define a secondcavity there between with the second chamber door. The second cavity canbe configured to receive a second enclosed biological substance, and thesecond agitator plate can be configured to pivot to agitate the secondenclosed biological substance.

In other aspects, a third heating assembly can be mounted on the firstagitator plate and a fourth heating assembly mounted on the secondagitator plate. The third and fourth heating assemblies can each havinga heater configured to selectively generate thermal energy torespectively heat first and second enclosed biological substancesdisposed within the housing. The first and second agitator plates withthe third and fourth heating assemblies mounted thereon can be linearlyslidable along the bottom side of the housing. The first and secondchambers doors can be mounted adjacent to the bottom side of the housingsuch that an upper portion of each of the first and second chambersdoors moves away from the top side of the housing to move to the openposition.

In another embodiment, a method for thawing a biological substance isprovided and includes pivoting a first chamber door on a first side of ahousing from a closed position to an open position to provide access toa first cavity within the housing, positioning a first enclosedbiological substance in a frozen state into the first cavity in thehousing, pivoting the first chamber door to the closed position to causea first heating assembly mounted on the first chamber door to contactthe first enclosed biological substance, and activating the firstheating assembly to cause a first heater of the first heating assemblyto generate thermal energy to heat the first enclosed biologicalsubstance from the frozen state to a fluid state.

In one aspect, when the first chamber door is moved to the closedposition, the first enclosed biological substance can be engaged betweenthe first heating assembly on the first chamber door and a secondheating assembly disposed within the housing. The method can furtherinclude activating the second heating assembly to cause a second heaterof the second heating assembly to generate thermal energy to heat thefirst enclosed biological substance from the frozen state to a fluidstate. The second heating assembly can be mounted on a first pivotingagitator plate, and the method can further include activating a firstagitation device to cause the first pivoting agitator plate to pivot andthereby agitate the first enclosed biological substance.

In other aspects, the method can include monitoring a temperature of atleast one of the first heating assembly and the first enclosedbiological substance. In yet another aspect, the method can includepivoting a second chamber door on a second side of a housing from aclosed position to an open position to provide access to a second cavitywithin the housing, and positioning a second enclosed biologicalsubstance in a frozen state into the second cavity in the housing. Athird heating assembly mounted on the second chamber door can beactivated to cause a third heater of the third heating assembly togenerate thermal energy to heat the second enclosed biological substancefrom the frozen state to a fluid state.

In one embodiment, a dry thawing system is provided and includes ahousing having a cavity configured to receive an enclosed biologicalsubstance, and a first heating assembly disposed within the housing andconfigured to be in thermal communication with an enclosed biologicalsubstance that is received within the cavity. The first heating assemblycan have a heater that is configured to selectively generate thermalenergy, and a heating cushion in thermal communication with the heater.The heating cushion can be configured to conduct thermal energygenerated by the heater. At least one temperature sensor can be disposedwithin the housing and configured to measure a temperature of at leastone of the heater and the heating cushion. The at least one temperaturesensor can be in communication with a power supply configured to supplyelectrical power to the heater, and the at least one temperature sensorcan be further configured to regulate power to the heater based upon themeasured temperature.

In one aspect, the at least one temperature sensor is configured tomeasure the temperature of the heater. When the measured temperatureexceeds a predetermined threshold temperature, the at least onetemperature sensor is further configured to transmit a failsafe signalto the power supply that is operative to cause the power supply toterminate delivery of power to the heater

In another aspect, the at least one temperature sensor is configured tomeasure the temperature of the heating cushion. When the measuredtemperature exceeds a predetermined threshold temperature, the at leastone temperature sensor is further configured to transmit a failsafesignal to the power supply that is operative to cause the power supplyto terminate delivery of power to the heater.

In one embodiment, the at least one temperature sensor can be a firsttemperature sensor that is configured to measure a temperature of theheater and a second temperature sensor that is configured to measure atemperature of the heating cushion. The first temperature sensor can beconfigured to transmit a first failsafe signal to the power supply whenthe measured temperature of the heater exceeds a predetermined firstthreshold temperature. The second temperature sensor can be configuredto transmit a second failsafe signal to the power supply when themeasured temperature of the heating cushion exceeds a predeterminedsecond threshold temperature. Receipt of either of the first and secondfailsafe signal by the power supply is operative to cause the powersupply to terminate delivery of power to the heater.

In other embodiments, the system can include the power supply. The powersupply can be configured to wirelessly communicate with the at least onetemperature sensor.

In another embodiment, a dry thawing system is provided and includes ahousing having a cavity configured to receive an enclosed biologicalsubstance, and a first heating assembly disposed within the housing andconfigured to be in thermal communication with an enclosed biologicalsubstance that is received within the cavity. The first heating assemblycan have a heater that is configured to selectively generate thermalenergy to heat an enclosed biological substance disposed within thecavity from a frozen state to a fluid state. At least one sensor can bedisposed within the housing and configured to detect at least oneparameter of an enclosed biological substance that is received withinthe cavity. A controller can be in communication with the at least onesensor, and the controller can be configured to communicate the at leastone parameter to a processor.

In one aspect, the processor can be one of a processor remote from thehousing and a processor disposed within the housing. In other aspects,the at least one parameter can be at least one of a date, a geographiclocation, and a time. In another aspect, the at least one parameter canbe data associated with a donor of a biological substance.

The at least one sensor can be configured to detect an authenticationtag that is coupled to an enclosed biological substance that is receivedwithin the cavity.

In other embodiments, at least one sensor can be disposed on a chamberdoor pivotally mounted to the housing, and the at least one sensor canbe configured to detect an authentication tag that is coupled to anenclosed biological substance that is received within the cavity.

In one embodiment, a dry thawing device is provided and includes ahousing having a cavity configured to receive an enclosed biologicalsubstance, and a first heating assembly disposed within the housing andconfigured to be in thermal communication with an enclosed biologicalsubstance received within the cavity. The first heating assembly canhave a heater that is configured to selectively generate thermal energy,and a fluid-filled cushion in thermal communication with the heater. Thefluid-filled cushion can be deformable and configured to selectivelytransfer the thermal energy generated by the heater to an enclosedbiological substance received within the cavity and in contact with thefluid-filled cushion.

In one aspect, the fluid-filled cushion includes a cushion body defininga compartment having at least one of a gel and water disposed therein.

In one embodiment, the cushion body includes an inner layer having afirst surface and a second surface, with the first surface defining thecompartment. The cushion body further includes a first barrier layerhaving a first surface and a second surface, with the first surface ofthe first barrier layer being disposed about at least a portion of thesecond surface of the inner layer, and the first barrier layer beingconfigured to substantially prevent egress of at least one of fluiddisposed in the compartment and vapor generated within the compartment.The cushion body can further include a second barrier layer that isdisposed about at least a portion of the second surface of the firstbarrier layer such that a first portion of the second barrier layercontacts the heater and a second portion of the barrier layer contactsan enclosed biological substance received within the cavity, with thesecond barrier layer being configured to inhibit the inner and firstbarrier layers from melting.

The device can also include an agitation device disposed within thehousing. The agitation device can be configured to cause the firstheating assembly to pivot about a pivot axis so as to agitate anenclosed biological substance received within the cavity. At least onebiasing element can bias the first heating assembly towards the cavityto cause the first heating assembly to be in thermal communication withan enclosed biological substance that is received within the cavity. Thedevice can also include a chamber door on the housing and pivotallymoveable between open and closed positions. A second heating assemblycam be coupled to the chamber door, and the second heating assembly canhave a second heater that is configured to be in thermal communicationwith an enclosed biological substance that is received within the cavitywhen the chamber door is in a closed position. The second heatingassembly can include a second fluid-filled cushion in thermalcommunication with the second heater, and the second fluid-filledcushion can be deformable and can be configured to selectively transferthe thermal energy generated by the second heater to an enclosedbiological substance received within the cavity and in contact withinthe second fluid-filled cushion. The second fluid-filled cushion of thesecond heating assembly can include a cushion body having a compartmentdefined therein, with the compartment of the second heating assemblyhaving at least one of a gel and water disposed therein.

In certain aspects, the second fluid-filled cushion of the secondheating assembly can include a cushion body having a compartment definedtherein that is configured to hold a fluid, with the cushion body of thesecond heating assembly including an inner layer having a first surfaceand a second surface, with the first surface defining the compartment.The cushion body of the second fluid-filled cushion can also include afirst barrier layer having a first surface and a second surface, withthe first surface of the first barrier layer being disposed about atleast a portion of the second surface of the inner layer, and the firstbarrier layer being configured to substantially prevent egress of atleast one of fluid disposed in the compartment and vapor generatedwithin the compartment. The cushion body of the second fluid-filledcushion can also include a second barrier layer that is disposed aboutat least a portion of the second surface of the first barrier layer suchthat a first portion of the second barrier layer contacts the heater anda second portion of the barrier layer contacts an enclosed biologicalsubstance received within the cavity, with the second barrier layerbeing configured to inhibit the inner and first barrier layers frommelting.

In other aspects, the device can include at least one temperature sensorthat is configured to measure a temperature of at least one of the firstheating assembly and an enclosed biological substance received withinthe cavity. In another aspect, the first heating assembly and thefluid-filled cushion can be removable and replaceable.

In another embodiment, a heating assembly for heating a biologicalsubstance is provided and includes a support member a heating assemblymounted on the support member and having a heater that is configured toselectively generate thermal energy, and a fluid-filled cushion mountedon the support member and in thermal communication with the heater, withthe fluid-filled cushion being deformable and configured to conductthermal energy generated by the heater.

The fluid-filled cushion can include a cushion body defining acompartment therein, the compartment having at least one of a gel andwater disposed therein. The cushion body can have an inner layer havinga first surface and a second surface, with the first surface definingthe compartment, a first barrier layer having a first surface and asecond surface, with the first surface of the first barrier layer beingdisposed about at least a portion of the second surface of the innerlayer, and the first barrier layer being configured to substantiallyprevent egress of at least one of fluid disposed in the compartment andvapor generated within the compartment, and a second barrier layer thatis disposed about at least a portion of the second surface of the firstbarrier layer such that a first portion of the second barrier layercontacts the heater and a second portion of the barrier layer isconfigured to contact a substance to be heated, with the second barrierlayer being configured to inhibit the inner and first barrier layersfrom melting.

In an embodiment, a method is provided. The method can includereceiving, within a chamber frame, an enclosed biological substance. Themethod can also include measuring, by a first temperature sensor, afirst temperature representing a temperature of a predetermined portionof at least one heating assembly. The at least one heating assembly canbe in thermal communication with the enclosed biological substancereceived within a chamber frame. The at least one heating assembly canalso be configured to selectively generate thermal energy in response toreceipt of a command signal. The method can further include measuring,by a second temperature sensor, a second temperature representing atemperature of the enclosed biological substance. The method canadditionally include measuring, by a weight sensor, a weight of theenclosed biological substance. The method can further include receiving,by a controller in communication with the at least one heating assembly,the first temperature, the second temperature, and the weight. Themethod can also include generating, by the controller, at least onecommand signal based upon the first temperature, the second temperature,and the weight.

In another embodiment, the controller can be configured to generate oneor more first command signals according to a first operation stage whena predetermined fraction of the enclosed biological substance is solid.The controller can also be configured to generate one or more secondcommand signals according to a second operation stage when apredetermined fraction of the enclosed biological substance is liquid.

In another embodiment, generating the one or more first command signalsby the controller can include receiving a first heating assembly setpoint temperature for the predetermined portion of the at least oneheating assembly, determining first proportional-integral-derivative(PID) settings based upon the weight of the enclosed biologicalsubstance, and generating the one or more first command signals basedupon the first PID settings and a difference between the firsttemperature measurement and the first heating assembly set pointtemperature.

In another embodiment, the first heating assembly set point can beselected from the range of about 37° C. to about 42° C.

In another embodiment, generating the one or more second command signalsby the controller includes receiving a second heating assembly set pointtemperature, different from the first heating assembly set pointtemperature, receiving second PID settings, different from the first PIDsettings, and generating the one or more second command signals basedupon the second PID settings and a difference between the firsttemperature measurement and the second heating assembly set pointtemperature.

In another embodiment, the method can further include, by thecontroller, receiving a transition temperature set point temperature forthe enclosed biological substance, and generating the one or more secondcommand signals after determining that the second temperature is aboutequal to the transition temperature.

In another embodiment, the transition temperature can be selected fromabout 5° C. to about 8° C.

In another embodiment, the method can further include, by thecontroller, receiving a final temperature for the enclosed biologicalsubstance and defining an end of the second operation stage when thesecond temperature measurement is about equal to the final temperature.

In another embodiment, the final temperature can be selected from about30° C. to about 37° C.

In another embodiment, the method can further include, by thecontroller, defining a thawing time elapsed from commencement of thefirst operating stage to a time prior to the end of the second operationstage, determining that the thawing time exceeds a predetermined maximumthawing time, and transmitting a command signal operative to cause theat least one heating assembly to cease generation of heat.

In another embodiment, after the end of the second operation stage, thecontroller can be configured to generate one or more third commandsignals according to a third operation stage operative to achieve apre-determined third heating assembly set point temperature.

In another embodiment, the method can further include, by thecontroller, receiving the third heating assembly set point temperature,receiving third PID settings, different from the first and second PIDsettings; and generating the one or more third command signals basedupon the third PID settings and a difference between the firsttemperature measurement and the third heating assembly set pointtemperature

In another embodiment, the method can further include, by thecontroller, defining a standby time elapsed from commencement of thethird operating stage, determining that the standby time exceeds apredetermined maximum standby time, and annunciating an alarm.

In another embodiment, the method can further include, by thecontroller, receiving a fourth heating assembly set point temperature,receiving fourth PID settings, and prior to generating the first orsecond command signals, generating one or more fourth command signalsbased upon the fourth PID settings and a difference between the firsttemperature measurement and the fourth heating assembly set pointtemperature.

In another embodiment, the fourth heating assembly set point can beselected from about 35° C. to about 40° C.

In another embodiment, the method can further include receiving theenclosed biological substance within the chamber frame afterdetermining, by the controller, that the first temperature measurementis about equal to the fourth heating assembly set point temperature.Receiving the enclosed biological substance can include opening achamber door pivotably mounted to a first end of a base of the chamberframe prior to the first operation stage.

In another embodiment, the method can further include, prior tomeasuring the weight of the enclosed biological substance, determiningby the controller that the chamber door is closed.

In another embodiment, the at least one heating assembly can includes aheater configured to selectively generate the thermal energy, and aheating cushion in thermal communication with the heater and theenclosed biological substance. The first temperature can be atemperature of the heating cushion.

In another embodiment, the at least one heating assembly can include afirst heating assembly and a second heating assembly. The first heatingassembly can be positioned adjacent to a first side of the enclosedbiological substance and the second heating assembly can be positionedadjacent to a second side of the enclosed biological substance, oppositethe first heating assembly.

In another embodiment, the method can further include axiallytranslating the first heating assembly along a base of the chamber frameto place the at least one heating assembly in thermal communication withthe enclosed biological substance.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other features will be more readily understood from thefollowing detailed description taken in conjunction with theaccompanying drawings, in which:

FIG. 1A is an exploded, front-view of one embodiment of a dry thawingchamber, illustrating a first heating assembly, a second heatingassembly, a bag assembly, and an agitation device mounted to a frame;

FIG. 1B is an exploded, rear-facing view of the dry thawing chamber ofFIG. 1A, illustrating the first heating assembly, the second heatingassembly, the bag assembly, and the agitation device mounted to theframe;

FIG. 2A is a isometric front-view of the dry thawing chamber of FIGS.1A-1B with a chamber door in a closed position;

FIG. 2B is an isometric front view of the dry thawing chamber of FIGS.1A-1B with the chamber door pivoted to an open position;

FIG. 2C is a side view of the dry thawing chamber of FIGS. 1A-1Billustrating sliding of the chamber door in the open position;

FIG. 2D is a side view of the dry thawing chamber of FIGS. 1A-1Billustrating sliding and pivoting of the chamber door in the openposition;

FIG. 3 is an exploded view illustrating the first heating assembly ofthe dry thawing chamber of FIGS. 1A-1B;

FIG. 4 is an exploded view illustrating the second heating assembly ofthe dry thawing chamber of FIGS. 1A-1B;

FIG. 5A is an exploded view illustrating the bag assembly of FIGS.1A-1B;

FIG. 5B is an isometric view illustrating the bag assembly of FIG. 5A;

FIG. 5C is a cross-sectional view illustrating an exemplary portion ofthe overwrap bag of FIGS. 5A-5B configured for thermal isolation of atemperature sensor;

FIG. 6 is a front side view of an embodiment of an overwrap bag having acompartment with a first funnel configuration;

FIG. 7 is a front side view of an another embodiment of an overwrap baghaving a compartment with a second funnel configuration;

FIG. 8A is a rear-facing isometric view of the dry thawing chamber ofFIGS. 1A-1B illustrating the agitation device in a first positionengaging the first heating assembly;

FIG. 8B is a rear-facing isometric view of the dry thawing chamber ofFIGS. 1A-1B illustrating the agitation device in a second positionengaging the first heating assembly;

FIG. 8C is a side view of the dry thawing chamber of FIG. 8A;

FIG. 8D is a side view of the dry thawing chamber of FIG. 8B;

FIG. 9A is a perspective view of another embodiment of a dry thawingsystem including two dry thawing chambers facing a common side;

FIG. 9B is a partially transparent perspective view of the dry thawingsystem of FIG. 9A;

FIG. 10A is a perspective view of another embodiment of a dry thawingsystem including two dry thawing chambers facing opposed sides;

FIG. 10B is a partially transparent perspective view of the dry thawingsystem of FIG. 10A;

FIG. 11A is a perspective view of another embodiment of a dry thawingsystem including first and second dry thawing chambers, illustrating thedry thawing system in a closed configuration;

FIG. 11B is a perspective of the dry thawing system of FIG. 11A,illustrating the dry thawing system in an open configuration;

FIG. 11C is a partial exploded view of a portion of the dry thawingsystem of FIG. 11B, illustrating the first and second dry thawingchambers;

FIG. 12 is a partial exploded view of a first chamber door and a firstheating assembly of the first dry thawing chamber of FIG. 11C;

FIG. 13A is a isometric view of a third heating assembly and supportmember of the first dry thawing chamber of FIG. 11C;

FIG. 13B is a partial exploded view of FIG. 13A;

FIG. 14 is a back view of an agitation device and chassis of the firstdry thawing chamber of FIG. 11C;

FIG. 15 is an exploded view of a mounting bracket of the first drythawing chamber of FIG. 11C;

FIG. 16A is side view of a portion of another embodiment of a drythawing chamber including a support frame, illustrating the supportframe in a first position;

FIG. 16B is a side view of the portion of the dry thawing chamber ofFIG. 16A, illustrating the support frame in a second position;

FIG. 17A is side view of a portion of another embodiment of a drythawing chamber including an agitator plate, illustrating the agitatorplate in a first position;

FIG. 17B is a side view of the portion of the dry thawing chamber ofFIG. 17A, illustrating the agitator plate in a second position;

FIG. 18A is a front view of an embodiment of a heating cushion;

FIG. 18B is a cross-sectional view of the heating cushion of FIG. 18Btaken at line B-B the facing a common side;

FIG. 19A is a schematic block diagram illustrating one exemplaryembodiment of a dry thawing system including a dry thawing chamberconfigured to thaw a biological substance based upon temperaturemeasurements acquired from one or more temperature sensors in a firstconfiguration;

FIG. 19B is a schematic block diagram illustrating another exemplaryembodiment of a dry thawing system including a dry thawing chamberconfigured to thaw a biological substance based upon temperaturemeasurements acquired from one or more temperature sensors in a secondconfiguration;

FIG. 19C is a schematic block diagram illustrating a further exemplaryembodiment of a dry thawing system including a dry thawing chamberconfigured to thaw a biological substance based upon temperaturemeasurements acquired from one or more temperature sensors in a thirdconfiguration;

FIG. 19D is a schematic block diagram illustrating a further exemplaryembodiment of a dry thawing system including a dry thawing chamberconfigured to thaw a biological substance based upon temperaturemeasurements acquired from one or more temperature sensors in a fourthconfiguration;

FIG. 19E is a schematic block diagram illustrating a further exemplaryembodiment of a dry thawing system including a dry thawing chamberconfigured to thaw a biological substance based upon temperaturemeasurements acquired from one or more temperature sensors in a fifthconfiguration;

FIG. 20 is a flow diagram illustrating one exemplary embodiment of amethod for pre-heating one or more selected dry thawing chambers;

FIG. 21 is a flow diagram illustrating one exemplary embodiment of amethod for determining parameters for closed-loop feedback control ofheating the selected dry thawing chambers based upon a weight of theenclosed biological substance;

FIG. 22 is a flow diagram illustrating one exemplary embodiment of amethod for thawing the enclosed biological substance;

FIG. 23 is a flow diagram illustrating one exemplary embodiment of amethod for monitoring a thawing time and a standby time;

FIG. 24 is a diagram illustrating an exemplary embodiment of aninterface for use by embodiments of the disclosed dry thawing systemsduring the pre-heating stage;

FIG. 25 is a diagram illustrating an exemplary embodiment of aninterface for use by embodiments of the disclosed dry thawing systems toselect the one or more dry thawing chambers;

FIG. 26 is a diagram illustrating an interface for use by embodiments ofthe disclosed dry thawing systems to input information regarding theenclosed biological substance;

FIG. 27 is a diagram illustrating an interface for use by embodiments ofthe disclosed dry thawing systems for monitoring a dry thawingoperation;

FIG. 28 is a diagram illustrating an interface for use by embodiments ofthe disclosed dry thawing systems to display information regarding acompleted dry thawing operation;

FIG. 29 is a diagram illustrating an interface for use by embodiments ofthe disclosed dry thawing systems to stop a dry thawing operation forremoval of an enclosed biological substance; and

FIG. 30 is a plot illustrating exemplary embodiments of measuredtemperatures and heating cushion power as a function of time during apre-heating stage, an ice stage, a liquid stage, and a standby stage.

It is noted that the drawings are not necessarily to scale. The drawingsare intended to depict only typical aspects of the subject matterdisclosed herein, and therefore should not be considered as limiting thescope of the disclosure.

DETAILED DESCRIPTION

Certain exemplary embodiments are described below to provide an overallunderstanding of the principles of the structure, function, manufacture,and use of the devices disclosed herein. One or more examples of theseembodiments are illustrated in the accompanying drawings. Those skilledin the art will understand that the devices specifically describedherein and illustrated in the accompanying drawings are non-limitingexemplary embodiments and that the scope of the present invention isdefined solely by the claims. The features illustrated or described inconnection with one exemplary embodiment may be combined with thefeatures of other embodiments. Such modifications and variations areintended to be included within the scope of the present invention.Further, in the present disclosure, like-named components of theembodiments generally have similar features, and thus within aparticular embodiment each feature of each like-named component is notnecessarily fully elaborated upon.

Existing systems for thawing enclosures containing a frozen biologicalsubstance (e.g., medication, plasma, glycerolized blood, red bloodcorpuscles (RBCs), etc.) operate by placing the bag in contact withheated water (e.g., water baths or water bladders). Heat is transferredfrom the water to the biological substance over a selected time durationto thaw the biological substance to a desired temperature range.However, these systems do not individually monitor the temperature ofeach bag for quality control during the thawing process. Typically, theambient temperature of the water bath or water bladder is monitoredduring the thawing process. Alternatively, at best, sampled quantitiesof biological substances are evaluated after thawing. Thus, it can bedifficult to achieve reproducible and consistent thawing of thebiological substances, creating opportunities for errors that can beharmful to patients.

Accordingly, dry thawing methods and devices are provided that canreceive enclosures containing biological substances and that can supplyheat to thaw the biological substance without an intermediate heatconducting fluid (e.g., water baths or water bladders). The applied heatcan be dynamically controlled based upon temperature measurementsacquired at or near a surface of the enclosure. Temperature measurementscan also be recorded to provide a complete temperature record during thethawing process.

Embodiments are discussed herein with respect to thawing biologicalsubstances, such as medications and blood. Examples of such biologicalsubstances can include, but are not limited to, whole blood, bloodproducts, plasma derivatives, mother's milk, ovaries, eggs, sperm,embryos, tissue, drugs, cells, such as chimeric antigen receptors t-cell(CAR-T) or other T-cells, molecular reagents, antibodies, etc.

In general, a dry thawing system can include at least one dry thawingchamber that is configured to receive an enclosed biological substance.In an exemplary embodiment, the at least one dry thawing chamber caninclude any one or more of a chamber frame, at least one heatingassembly, an agitator device configured to agitate the enclosedbiological substance, and at least one temperature sensor. The at leastone heating assembly can include a heater that is configured to heat theenclosed biological substance disposed within the chamber frame. The atleast one temperature sensor can be configured to monitor thetemperature of the enclosed biological substance.

Dry Thawing Chamber

FIGS. 1A-1B illustrate one exemplary embodiment of a dry thawing chamber200. As shown, the dry thawing chamber 200 includes a chamber frame 202having a top portion 204, a bottom portion 206, a first sidewall 208,and a second sidewall 210 opposite the first sidewall 208. The first andsecond sidewalls 208, 210 extend between the top portion 204 and thebottom portion 206. A first heating assembly 400 is pivotally mountedproximate to a first end 212 (e.g., rear end) of the chamber frame 202,about a first pivot 426. A second heating assembly 500 is pivotallymounted to a second end 214 (e.g., front end) of the chamber frame 202,opposite the first end 212, about a second pivot 526. A bag assembly 600can be removably disposed within a cavity formed between the firstheating assembly 400 and the second heating assembly 500 in order to bein thermal communication with a heater 408 of the first heating assembly400 and a heater 508 of the second heating assembly 500. As shown inFIGS. 1A and 1B, and in more detail in FIGS. 5A-5C, the bag assembly 600includes a biological substance 602 disposed within an enclosure 604that is further disposed within an overwrap bag 606, as will bediscussed in more detail below.

The chamber frame 202 can have a variety of configurations. In theillustrated embodiment, the chamber frame 202 includes a cross-member222 mounted to the sidewalls 208, 210 and an agitation device 224mounted to the cross-member 222. As discussed below, so positioned, theagitation device 224 can contact a rear-facing surface 422 of the firstheating assembly 400 to cause pivotal movement of the first heatingassembly 400 about the first pivot 426.

Optionally, the dry thawing chamber 200 can include a mechanism forestimating the weight and/or volume of the bag assembly 600, and thusthe enclosed biological substance 602. In one embodiment, as shown inFIGS. 1A and 1B, the dry thawing chamber 200 includes one or more weightmeasuring sensors 226 (e.g., load cell[s] [LC]) for measuring a weightof the bag assembly 600. As an example, the weight measuring sensor 226can be provided in communication with one or more of the mounting posts228, 230. Thus, when the bag assembly 600 is positioned within the drythawing chamber 200 and supported by the mounting posts 228, 230, anaccurate measurement of the weight of the bag assembly 600 can beobtained.

This measured weight can be transmitted to a controller fordetermination of the weight of the enclosed biological substance 602. Inone aspect, the controller can determine the weight of the enclosedbiological substance 602. In embodiments where the weight of theenclosure 604 and the overwrap bag 606 are negligible compared to theweight of the enclosed biological substance 602, the measured weight canbe approximately equal to the weight of the enclosed biologicalsubstance 602. In embodiments where the weight of the enclosure 604 andthe overwrap bag 606 are not negligible compared to the weight of theenclosed biological substance 602, the controller can subtract theweights of the enclosure 604 and the overwrap bag 606 from the measuredweight to obtain the weight of the enclosed biological substance 602.The weights can be obtained by the controller from a data storage deviceor input by an operator of the dry thawing system using an userinterface device.

Alternatively or additionally, the controller can be configured toestimate a volume of the enclosed biological substance 602 based uponthe determined weight of the enclosed biological substance 602. In oneaspect, the controller can use a density of the enclosed biologicalsubstance 602 to determine the volume of the enclosed biologicalsubstance 602. In another aspect, the controller can use a lookup tableto determine the volume of the enclosed biological substance 602. Thedensity and/or lookup table can be obtained by the controller from adata storage device or input by an operator of the dry thawing systemusing an user interface device.

As indicated above, the first heating assembly 400 can be pivotablymounted to the chamber frame 202. For example, as shown in FIGS. 1A-1B,the first heating assembly 400 includes a first pivot 426. While thefirst pivot 426 can have a variety of configurations, as shown, thefirst pivot 426 is in the form of two pivot pins each extendinglaterally outward from opposing sides of the first heating assembly 400.The chamber frame 202 includes a first pivot mount 232 that is in theform of a first pivot bore extending through a first sidewall 208 of thechamber frame 202 and a second pivot bore extending through the secondsidewall 210 of the chamber frame 202. The first pivot mount 232 isconfigured to receive the first pivot 426. When the first heatingassembly 400 is mounted to the first pivot mount 232, at least a portionof the first heating assembly 400 can be positioned between the firstand second sidewalls 208, 210. So configured, the first heating assembly400 forms a planar structure mounted proximate to the first end 212(e.g., rear end) of the chamber frame 202.

The location of the first pivot 426 and first pivot mount 232 can beselected along the height of the first heating assembly 400 and thechamber frame 202. As shown, the first pivot 426 and the first pivotmount 232 are positioned at a location roughly centered along the heightof the first heating assembly 400 and the first and second sidewalls208, 210 of the chamber frame 202, respectively. However, alternativeembodiments of the dry thawing chamber 200 can include the first pivot426 and first pivot mount 232 at other locations, such as adjacent tothe top portion 204 or bottom portion 206 of the chamber frame 202. Asdiscussed in greater detail below, the pivoting engagement of the firstheating assembly 400 and chamber frame 202 allows the agitation device224, also mounted to the chamber frame 202, to mechanically engage thefirst heating assembly 400 and urge it to pivot.

The second heating assembly 500 can be part of or can form the chamberdoor 302 and the chamber door 302 can be pivotably mounted to thechamber frame 202. For example, the second heating assembly 500 caninclude a second pivot 526. While the second pivot 526 can have avariety of configurations, as shown, the second pivot 526 is in the formof two pivot pins each extending laterally outward from opposing sidesof the second heating assembly 500. The chamber frame 202 includes asecond pivot mount 238 that is in the form of a first pivot boreextending through a first sidewall 208 of the chamber frame 202 and asecond pivot bore extending through the second sidewall 210 of thechamber frame 202. The second pivot mount 238 is configured to receivethe second pivot 526.

The location of the second pivot 526 and second pivot mount 238 can beselected along the length of the second heating assembly 500 and thechamber frame 202. As shown, the second pivot 526 and the second pivotmount 238 are positioned at locations adjacent to an end 536 (e.g., abottom end) of the second heating assembly 500 and the bottom portion206 of the chamber frame 202, respectively. So configured, the secondheating assembly 500 forms a planar structure mounted to a second end214 (e.g., front end) of the chamber frame 202, opposite the first end212.

As shown in FIGS. 2A-2B, this configuration can allow the chamber door302 to pivot about the second pivot 526, denoted by arrow 311, betweenan open position and a closed position. In the open position (FIG. 2B),the upper portion of the chamber door 302 moves away from the chamber toexpose a cavity 304 defined between the chamber frame 202, the firstheating assembly 400, and the second heating assembly 500. Thus, whenthe chamber door 302 is in the open position, the cavity 304 isaccessible from outside of the dry thawing chamber 200 and an bagassembly 600 can be inserted between the first heating assembly 400 andsecond heating assembly 500. In the closed position (FIG. 2A), thecavity 304 becomes sealed from the exterior of the dry thawing chamber200 (a sealed cavity). The sealed cavity can be dimensioned toaccommodate the bag assembly 600 including the overwrap bag 606, theenclosure 604, and the enclosed biological substance 602 containedtherein. Furthermore, in the closed position, the bag assembly 600received within the sealed cavity is positioned in contact with heatingcushions 404, 504 of the first and second heating assemblies 400, 500and adjacent to heaters 408, 508, respectively.

The chamber door 302 and chamber frame 202 can include at least onelatching mechanism to lock the chamber door 302 in the closed positionduring use. As shown in FIGS. 2A-2B, the chamber door 302 and thechamber frame 202 include first and second latching mechanisms 306, 308.While the first and second latching mechanisms 306, 308 can have avariety of configurations, in the illustrated embodiment the first andsecond latching mechanisms 306, 308 are structurally similar and eachinclude a latching member 310, 312 and a receiving member 314, 316. Asshown in FIGS. 2A-2B, each latching member 310, 312 includes aprotrusion 318, 320 extending outwardly therefrom and through a flange319, 321 extending outwardly from the chamber door 302. Each receivingmember 314, 316 in the form of a flange 322, 324 extending outwardlyfrom the chamber frame 202 and includes a bore 326, 328 extendingtherethrough. The bores 326, 328 are configured to receive theprotrusion 318, 320 of corresponding latching members 310, 312. In otherembodiments, other latching mechanisms can be used.

As further illustrated in FIGS. 2C-2D, the chamber door 302 can beconfigured to linearly slide towards and away, denoted by arrow 313,from the chamber frame 202. As an example, the portion of the chamberframe 202 including the second pivot mount 238 can include telescopingrails (not shown) or other sliding mechanisms. By sliding the chamberdoor 302 away from the chamber frame 202, as denoted by arrow 313, aloneor in combination with pivoting, as denoted by arrow 311, additionalspace can be provided for inserting the bag assembly 600 within the drythawing chamber 200.

Heating Assembly

Each heating assembly can have a variety of configurations. FIG. 3 is anexploded, isometric view of the first heating assembly 400. As shown,the first heating assembly 400 includes, from front to rear, a firstassembly frame 402, the heating cushion 404 with a contact temperaturesensor 405 coupled thereto, a second assembly frame 406, the heater 408,an isolator 410, and a cover 412. The contact temperature sensor 405 canbe similar to third contact temperature sensor 130 shown in FIGS. 19Aand 19C-19E. The isolator 410 can be a generally flexible, planarstructure that possesses a relatively low thermal conductivityconfigured to inhibit transfer of heat from the heater 408 to the cover412. As an example, the isolator 410 can be formed from materials suchas one or more of polystyrene foam, starch-based foams, cellulose,paper, rubber, and plastic. The heater 408 can be a generally flexible,planar structure that is configured to generate heat. In certainembodiments, the heater 408 can be a resistive heater that generatesheat in response to receipt of electrical current. The heating cushion404 can include a cushion body 414 and a lip 416 extending laterallyoutward from an outer periphery of the cushion body 414.

When the first heating assembly 400 is assembled, the cover 412 iscoupled to the second assembly frame 406. The heater 408 can bepositioned within or adjacent to the aperture 418 of the second assemblyframe 406, with the isolator 410 interposed between the cover 412 andthe heater 408. The second assembly frame 406 is further coupled to thefirst assembly frame 402. The heating cushion lip 416 can be positionedbetween the second assembly frame 406 and the first assembly frame 402and secured thereto (e.g., by friction, one or more fasteners,adhesives, etc.). At least a portion of the heating cushion body 414 canextend through the aperture 420 of the first assembly frame 402. Soassembled, the cover 412 forms a generally planar, rigid rear-facingsurface 422 of the first heating assembly 402, as shown in FIG. 1A, thecushion body 414 forms a deformable front-facing surface 424 of thefirst heating assembly 402, as shown in FIG. 1B, and heat can beconducted from the heater 408 to the exterior surface of the cushionbody 414.

The second heating assembly 500 can be formed and assembled similarly tothe first heating assembly 400. As shown in FIG. 4, the second heatingassembly 500 includes, from front to rear, the cover 512, the isolator510, the heater 508, the second assembly frame 506, the heating cushion504 with a contact temperature sensor 505 coupled thereto, and the firstassembly frame 502. So assembled, the cover 512 and second assemblyframe 506 form a front-facing surface 524 of the second heating assembly500 (e.g., the chamber door 302), as shown in FIG. 1A, while the cushionbody 514 forms a deformable rear-facing surface 522 of the secondheating assembly 500, as shown in FIG. 1B, and heat can be conductedfrom the heater 508 to the exterior surface of the cushion body 514. Thecontact temperature sensor 505 can be similar to fourth contacttemperature sensor 132 shown in FIGS. 19A and 19C-19E.

The cushion body 414 can be formed from a material having a relativelyhigh thermal conductivity configured to permit transfer of heat from theheater therethrough. In further embodiments, the cushion body 414 can beformed from a reversibly deformable material. As an example, the cushionbody 414 can be filled with a fluid. Non-limiting examples of suitablefluids include water, gel, synthetic oils, non-synthetic oils, otherheat-absorbing materials, or any combination thereof.

In other embodiments, the heating cushion can be formed of a singlelayer or multiple layers (e.g., two or more layers). For example, asshown in FIG. 18A-18B, a heating cushion 1900 can include amulti-layered cushion body 1902 defining a compartment 1904 therein thatis configured to house a fluid. In this illustrated embodiment, themulti-layered cushion body 1902 includes an inner layer 1906, a firstbarrier layer 1908, and a second barrier layer 1910. Each layer can havea variety of thickness. In some embodiments, each layer can have athickness from about 1 μm to 100 μm, about 1 μm to 35 μm, about 1 μm to33 μm, about 1 μm to 20 μm, or about 10 μm to 15 μm.

The inner layer 1906 has a first surface 1906 a and a second surface1906 b, in which the compartment 1904 is bounded by the first surface1906 a. The inner layer can formed of any suitable flexible material.Non-limiting examples of suitable flexible materials includepolyethylene, other polymeric materials having multi-axis flexibility,or any combination thereof.

The first barrier layer 1908 has a first surface 1908 a and a secondsurface 1908 b. The first barrier layer 1908 is configured tosubstantially prevent egress of fluid disposed in the compartment 1904and/or vapor generated within the compartment 1904 during use. In thisillustrated embodiment, the first barrier layer 1908 is disposed ontothe second surface 1906 b of the inner layer 1906. In other embodiments,the first barrier layer 1908 can be disposed onto a portion of thesecond surface 1906 b of the inner layer 1906. Non-limiting example ofsuitable materials for the first barrier layer include methyl aluminumoxide, and the like, and any combination thereof.

The second barrier layer 1910 is configured to inhibit the inner andfirst barrier layers 1906, 1908 from melting. For example, the secondbarrier layer 1910 can inhibit melting of the inner and first barrierlayers 1906, 1908 in response to the generation of a hot spot or spotsbetween the heater and the heating cushion 1900. A hot spot or spots canbe generated, for example, as a result of pressure created by a frozenenclosed biological substance, which can expand the heating cushion. Asa result, this expansion can further compress the heating cushionagainst the heater, and thus generate a hot spot or spots at theirinterface. Further, the second barrier layer 1910 is configured topermit transfer of a relatively high flux of heat therethrough from afluid disposed within the compartment 1904 of the multi-layered heatingcushion body 1902.

In this illustrated embodiment, the second barrier layer 1910 isdisposed onto the second surface 1908 b of the first barrier layer 1908such that a first portion 1910 a of the second barrier layer 1910contacts a heater and a second portion 1910 b of the second barrierlayer 1910 contacts an enclosed biological substance received within acavity formed between heating assemblies, like first and second heatingassemblies 400, 500 shown in FIGS. 1A-1B and 3-4 or first and thirdheating assemblies 1208, 1242 shown in FIGS. 11C-13B. In otherembodiments, the second barrier layer 1910 can be disposed onto aportion of the second surface 1908 b of the first barrier layer 1908.

The second barrier layer 1910 can have a melting point that is greaterthan the melting points of the inner and first barrier layers 1906,1908. For example, in some embodiments, the second barrier layer 1910has a melting point from about from about 80° C. to 200° C. Non-limitingexamples of suitable materials for the second barrier layer 1910 includebiaxially oriented polyamide (BOPA), or the like, or any combinationthereof.

In certain embodiments, a multi-layered cushion body can include twolaminates partially sealed, e.g. heated sealed, together. Each laminatecan have an inner layer, like inner layer 1906 as shown in FIG. 18B, afirst barrier layer, like first barrier layer 1908 as shown in FIG. 18B,and a second barrier layer, like second barrier layer 1910 as shown inFIG. 18B. As such, a portion of the inner layers can form a compartmentdefined within the cushion body, and the second barrier layers can formopposing outer surfaces of the cushion body. Each laminate can have avariety of thickness. For example, in some embodiments, each laminatecan have a thickness from about 1 μm to 50 μm, or from about 1 μm to 40μm. In other embodiments, each laminate can have a thickness of about 40μm or of about 50 μm.

Bag Assembly

The bag assembly can also have a variety of configurations, and variousbags can be used with the systems and methods disclosed herein. FIGS.5A-5B illustrate one exemplary embodiment of a bag assembly 600. Asshown, the bag assembly includes a biological substance 602 disposed inthe enclosure 604 which is disposed within the overwrap bag 606. Theoverwrap bag 606 can be in the form of a reversibly sealable pouchdimensioned to receive the enclosure 604. In the event that theenclosure 604 leaks or ruptures during the thawing process, the overwrapbag 606 can isolate the biological substance 602, thereby preventingcontamination of the dry thawing system.

The overwrap bag 606 can be configured to satisfy one or more functionalrequirements. In one aspect, the overwrap bag 606 can possess arelatively high thermal conductivity to facilitate heating of theenclosure 604 and biological substance 602 contained therein. In anotheraspect, the overwrap bag 606 can be configured to withstand temperatureswithin a predetermined temperature range (e.g., about −196° C. to about40° C.). In a further aspect, the overwrap bag 606 can be disposableafter a single use or formed from materials capable of being sterilizedand reused in accordance with the requirements of domestic and/orinternational governing organizations and regulatory bodies. In anadditional aspect, the overwrap bag 606 can be configured to provideanti-microbial properties, whether intrinsically or through the use ofcoatings or additives. Examples of materials forming the overwrap bag606 can include plastics, metals, and combinations thereof.

The overwrap bag 606 can be soft, semi-rigid, or rigid and dimensionedto receive enclosures of any size. For example, as shown in FIGS. 6 and7, a compartment or cavity 1002, 1102 of an overwrap bag 1000, 1100 canbe dimensioned so as to have a funnel-shaped configuration. Further, insome embodiments, an overwrap bag can include a RFID (e.g., mounted toan outer surface), such as RFID tag 601 mounted to overwrap bag 606 asshown in FIGS. 1A-1B and 5A-5B, RFID tag 1001 mounted to overwrap bag1000 shown in FIG. 6, and RFID tag 1101 mounted to overwrap bag 1100 asshown in FIG. 7. Exemplary embodiments of RFID tags are described inmore detail in International Patent Application No. WO 2016/023034,which is hereby incorporated by reference in its entirety.

In certain embodiments, the enclosure can be a blood bag having a volumewithin the range from about 100 mL to about 500 mL. In otherembodiments, as shown in FIG. 7, the enclosure 1104 can be in the formof a vial, which can contain a biological substance such as blood,cells, sperm, tissue, and the like. While the volume of the vial will bedependent at least upon the dimensions of the overwrap bag, in someembodiments, the vial can have a volume in a range of about 3 mL toabout 10 mL. The volume of the heating cushion (e.g., like heatingcushions 404, 504) and/or the elastic properties (e.g., elastic modulus)of the heating cushion (e.g., like heating cushions 404, 504) can beconfigured to accommodate the shape and volume of the enclosure,regardless of size, ensuring contact between the enclosure and theheating cushions and good conduction of heat between the heatingcushions and the biological substance.

The overwrap bag 606 can include an overwrap body 608 and a cover 610attached to one end of the overwrap body 608 (e.g., a top end). Thecover 610 can be configured to open and close, allowing insertion of theenclosure 604 within the overwrap body 608 when open and hermeticsealing of the overwrap body 608 when closed for protection ofenclosures, like enclosure 604, placed therein. In certain embodiments,the cover 610 can be formed from a biologically inert material, such asan epoxy. The cover 610 can further include a closure mechanism to formthe hermetic seal. The closure mechanism can be embedded and/orintegrally formed with the cover 610. Examples of closure mechanisms caninclude interlocking grooves and ridges, reversible adhesives,magnetic-based closures, etc.

The cover 610 can be configured to engage the chamber frame 202 forsupport of the bag assembly 600. As an example, the cover 610 can beformed in the shape of hooks 612, 614 at opposed lateral ends. The hooks612, 614 can rest on mounting posts 228, 230 positioned adjacent the topportion 204 of the chamber frame 202 to suspend the bag assembly 600 inplace when inserted within the dry thawing chamber 200. In certainembodiments, the overwrap bag 606 can be in the form of an overwrap bagas discussed in previously mentioned International Patent ApplicationNo. WO 2016/023034, which is incorporated herein in its entirety.

The overwrap bag 606 can be further configured to facilitate temperaturemeasurements of the enclosed biological substance 602. FIG. 5Cillustrates a cross-sectional view of an exemplary portion of theoverwrap bag 606, where a contact temperature sensor 620 is positionedon an inward facing surface 622 of the overwrap bag 606. Opposing thetemperature sensor 620 on an exterior facing surface 624 of the overwrapbag 606 is an encapsulated air pocket 626. The air pocket 626 can act asan insulator, promoting thermal isolation of the temperature sensor 620from the environment external to the overwrap bag 606. In furtherembodiments, the encapsulation 628 can be formed from a material havinga low thermal conductivity, further promoting thermal isolation of thetemperature sensor 620.

In further embodiments (not shown), a dry thawing chamber, like drythawing chamber 200 shown in FIGS. 1A-1B, can include a vacuummechanism, such as a vacuum pump in fluid communication with an interiorof the overwrap body (e.g., via a one-way valve). When the chamber dooris placed in the closed position, the vacuum pump can be activated toremove air from the interior of the overwrap body and create a partialvacuum within the overwrap body. By reducing the pressure within theoverwrap body, as compared to the ambient pressure outside the overwrapbody, the overwrap body can be urged into contact with the enclosure bythe ambient pressure. In this manner, the accuracy of temperaturemeasurements acquired by temperature sensor(s) mounted to the overwrapbody can be improved.

Agitator

As indicated above, an agitator can be disposed within the chamber framefor agitating an enclosed biological substance during heating. Theagitator can have a variety of configurations. FIGS. 8A-8D illustrateone exemplary embodiment of an agitation device 224 configured toagitate the enclosed biological substance (not shown) contained withinthe bag assembly 600 placed within the dry thawing chamber 200. Asshown, the agitation device 224 can be mounted to the chamber frame 202and it can include a motor 702 and a cam 704. The cam 704 is positionedin contact with the cover 412 of the first heating assembly 400 at apredetermined distance from the first pivot 426. When the agitationdevice 224 is activated, the motor 702 causes the cam 704 to rotate andmake sliding contact with the cover 412. This contact imparts reciprocalmotion to the first heating assembly 400 and causes the first heatingassembly 400 to reversibly pivot about the first pivot mount 232. Thatis, opposing ends (e.g., top and bottom ends) of the first heatingassembly 400 can oscillate relative to the chamber frame 202.

Because the second heating assembly 500 is fixed in place when in theclosed position, the pivoting motion of the first heating assembly 400alternates application of a compressive force against opposed ends ofthe bag assembly 600 (e.g., top and bottom ends) and agitates theenclosed biological substance (not shown) as it thaws. As shown in FIGS.8A and 8C, when the cam 704 extends towards the first heating assembly400, it urges the first heating assembly 400 to pivot clockwise, towardsa bottom end 520 of the second heating assembly 500. A bag assembly 600positioned between the first and second heating assemblies 400, 500 thusexperiences a compressive force at its bottom end that urges theenclosed biological substance (not shown) upwards. As further shown inFIGS. 8B and 8D, when the cam 704 retracts away from the first heatingassembly 400, the enclosed biological substance (not shown) is no longerurged towards the top portion 204 of the chamber frame 202 and movesdownwards, towards the bottom portion 206 of the chamber frame 202,under the force of gravity. In response, the first heating assembly 400pivots counterclockwise, towards a top end 518 of the second heatingassembly 500. The bag assembly 600 positioned between the first andsecond heating assemblies 400, 500 thus experiences a compressive forceat its top end that further urges the enclosed biological substance (notshown) downwards.

The frequency and magnitude at which the agitation device 224 drives thefirst heating assembly 400 to alternate application of compressive forceagainst opposed ends of the bag assembly 600 can be controlled by thecontroller (e.g., controller 104). In one example, the RPM of the motor702 of the agitation device 224 can be increased to increase thefrequency of agitation and decreased to decrease the frequency of theagitation. In another example, the amplitude of the agitation can berelated to the radius of the cam 704 of the agitation device 224.

Housing

One or more of the aforementioned dry thawing chambers can be containedwithin a housing, such as a portable housing. FIGS. 9A-9B illustrate afirst exemplary embodiment of a dry thawing system 800 including ahousing or chassis 802 containing a first dry thawing chamber 804, likedry thawing chamber 200 shown in FIGS. 1A-2D and 8A-8D, and a second drythawing chamber 806, like dry thawing chamber 200 shown in FIGS. 1A-2Dand 8A-8D, in communication with a power supply 808. The power supply808 can be configured to supply power to the first and second drythawing chambers 804, 806. Each of the dry thawing chambers 804, 806 canbe arranged with chamber doors 809, 811 facing a common side of thechassis 802 (e.g., a front side 810). A first door 812 and a second door814 of the chassis 802 can be coupled to the chamber door 809 of thefirst dry thawing chamber 804 and the chamber door 811 of the second drythawing chamber 806, respectively, allowing an operator to insert orremove a bag assembly, like bag assembly 600 shown in FIGS. 1A-1B and5A-5B, from respective dry thawing chambers. A handle 816 is alsocoupled to the chassis 802, allowing the dry thawing system 800 to beeasily carried. The handle 816 can be configured to fold into a recesswithin the chassis 802 when not being carried.

In some embodiments, an indicator light can be provided to indicate astatus of a dry thawing chamber. For example, as shown in FIG. 9A, afirst indicator light 818 can be provided to indicate a status of thefirst dry thawing chamber 804 and a second indicator light 820 can beprovided to indicate a status of the second dry thawing chamber 806, asdiscussed below. Fewer (e.g., one) or more (e.g., three or more)indicator lights can be provided according to how many dry thawingchambers are contained within a dry thawing system.

The user interface 822 can be mounted to a common side (e.g. front side810) of the chassis 802 and it can receive power from the power supply808. In certain embodiments, the user interface 822 can also include acontroller. In alternative embodiments, the user interface 822 can beconfigured to communicate with a remote controller.

The user interface 822 can, for example, be a cathode ray tube (CRT)and/or a liquid crystal display (LCD) monitor. The interaction with anoperator user can, for example, be a display of information to theoperator and a keyboard and a pointing device (e.g., a mouse, trackball,optical or resistive touch screen, etc.) by which the operator canprovide input to the computer (e.g., interact with a user interfaceelement). Other kinds of devices can be used to provide for interactionwith an operator. Other devices can, for example, be feedback providedto the operator in any form of sensory feedback (e.g., visual feedback,auditory feedback, or tactile feedback). Input from the operator can,for example, be received in any form, including acoustic, speech, and/ortactile input.

The controller can be configured to provide commands to a heater, likeheater 408 and/or heater 508 shown in FIGS. 1A-4, and an agitationdevice, like agitation device 224 shown in FIGS. 1A-1B and 8A-8D, inaccordance with a predetermined thawing program. The predeterminedthawing program can include a target temperature-time response of atleast one heating cushion, like heating cushions 404, 504 shown in FIGS.1A-4, and an enclosed biological substance, like enclosed biologicalsubstance 602 shown in FIGS. 1A-1B and 5A-5B. As an example, an operatorcan employ the user interface device to select the predetermined thawingprogram from a list of predetermined thawing programs stored by a datastorage device in communication with the controller.

In other embodiments, the predetermined thawing program can be selectedautomatically by the controller from a list of predetermined thawingprograms. As an example, the predetermined thawing program can beselected by the controller based upon a volume or weight of the enclosedbiological substance.

The controller can receive the volume and/or weight of the enclosedbiological substance in a variety of ways. In one aspect, the controllercan receive the volume and/or weight from manual input by an operatorusing the user interface device. In another aspect, the user interface822 can include an input device 824, such as a barcode reader or otherautomated input device (e.g., an optical character reader, aradiofrequency tag reader, etc.) and the input device can read thevolume of the enclosed biological substance from markings on enclosureitself representing the volume and/or weight (e.g., a barcode, text) ora device secured to the enclosure (e.g., an RFID tag) thatelectronically stores data including the volume and/or weight In afurther embodiment, the controller can obtain the volume and/or weightfrom weight measurements of the overwrap bag when positioned in the drythawing chamber, as discussed above.

The controller can be implemented in digital electronic circuitry, incomputer hardware, firmware, and/or software. The implementation can beas a computer program product. The implementation can, for example, bein a machine-readable storage device, for execution by, or to controlthe operation of, data processing apparatus. The implementation can, forexample, be a programmable processor, a computer, and/or multiplecomputers.

A computer program can be written in any form of programming language,including compiled and/or interpreted languages, and the computerprogram can be deployed in any form, including as a stand-alone programor as a subroutine, element, and/or other unit suitable for use in acomputing environment. A computer program can be deployed to be executedon one computer or on multiple computers at one site.

Processors suitable for the execution of a computer program include, byway of example, both general and special purpose microprocessors, andany one or more processors of any kind of digital computer. Generally, aprocessor receives instructions and data from a read-only memory or arandom access memory or both. The essential elements of a computer are aprocessor for executing instructions and one or more memory devices forstoring instructions and data. Generally, a computer can include, can beoperatively coupled to receive data from and/or transfer data to one ormore mass storage devices for storing data (e.g., magnetic,magneto-optical disks, or optical disks).

Information carriers suitable for embodying computer programinstructions and data include all forms of non-volatile memory,including by way of example semiconductor memory devices. Theinformation carriers can, for example, be EPROM, EEPROM, flash memorydevices, magnetic disks, internal hard disks, removable disks,magneto-optical disks, CD-ROM, and/or DVD-ROM disks. The processor andthe memory can be supplemented by, and/or incorporated in specialpurpose logic circuitry.

FIGS. 10A-10B illustrate a second exemplary embodiment of a dry thawingsystem 900 including a chassis 902 containing two dry thawing chambers904, 906 in communication with a power supply 908. Each of the drythawing chambers 904, 906 are arranged with chamber doors 909, 911facing opposed sides of the chassis (e.g., left and right sides 910 a,910 b). First and second doors 911, 912 of the chassis 902 can becoupled to the first and second chamber doors 909, 911, respectively,allowing an operator to insert or remove a bag assembly, like bagassembly 600 shown in FIGS. 1A-1B and FIGS. 5A-5B, from respective drythawing chambers. The user interface 920 (e.g., a touch-screen display)can also be mounted to another side of the chassis 902 (e.g., a frontside 910 c), in between the two dry thawing chambers. The second drythawing system embodiment can also include a handle 914, indicatorlights 916, 918, a user interface 920, a controller similar to the firstdry thawing system 800 as shown in FIGS. 9A-9B.

In certain embodiments, the portable dry thawing systems 800, 900 ofFIGS. 9A-9B and 10A-10B can include dry thawing chambers that areremovable from their respective housings. As an example, each drythawing chamber can be received within a socket (not shown) formedwithin its housing. A wiring harness or electrical contacts can bepositioned within the sockets and configured to reversibly mate with acorresponding wiring harness or electrical contacts of the dry thawingchamber. Power, command signals, and measured temperatures can betransmitted between the power supply, controller, and dry thawingchamber via the wiring harnesses and/or electrical contacts. Soconfigured, dry thawing chambers can be removed from the housing forsterilization, disinfection, repair, and/or replacement.

FIGS. 11A-11C illustrate another embodiment of a dry thawing system 1200that includes a housing or chassis 1201 containing a first dry thawingchamber 1202 a and a second dry thawing chamber 1202 b in communicationwith a power supply 1226. The chassis 1201 has a main body 1203 withfirst and second opposing, doors 1204 and 1206 pivotally mounted atfirst and second ends 1203 a, 1203 b thereof. A handle 1205 is alsocoupled to the chassis 1201, allowing the dry thawing system 1200 to beeasily carried.

The first and second doors 1204, 1206 serve as a chamber door of thefirst and second dry thawing chambers 1202 a, 1202 b 1203 b,respectively, thereby allowing an operator to insert or remove anenclosed biological substance from respective dry thawing chambers. Eachfirst and second doors 1204, 1206 has a first heating assembly 1208 anda second heating assembly 1210, respectively, coupled thereto. Each door1204, 1206 is structurally similar and each first and second heatingassemblies 1208, 1210 is structurally similar, and therefore, for thesake of simplicity, the following description is with respect to thefirst door 1204 and the first heating assembly 1208 coupled thereto. Aperson skilled in the art will understand, however, that the followingdiscussion is also applicable to the second door 1206 and the secondheating assembly 1210 coupled thereto.

As shown in more detail in FIG. 12, the first door 1204 includes anouter cover 1212 and inner cover 1214 The first heating assembly 1208includes a heater 1216 and a heating cushion 1218 coupled thereto. Whilethe heater 1216 can have a variety of configurations, as shown, theheater 1216 is in the form of a heater plate. At least one temperaturesensor 1220 is coupled to an outer surface 1218 a of the heating cushion1218, and therefore in thermal communication therewith. As such, theillustrated at least one temperature sensor 1220 is configured tomeasure the temperature of the heating cushion 1218 during use. Whilethe at least one temperature sensor 1220 can have a variety ofconfigurations, in this illustrated embodiment, the at least onetemperature sensor 1220 includes two temperature sensors, a thermistor,e.g., a NTC thermistor, and a thermocouple. In certain embodiments, oneof the two temperature sensors can be in communication with the powersupply 1226 that is configured to supply electrical power to the heater1216. In such instances, when the measured temperature of the heatingcushion 1218 exceeds a predetermined threshold temperature, the one ofthe two temperature sensors can transmit a failsafe signal to the powersupply 1226 that is operative to cause the power supply 1226 uponreceipt to terminate delivery of power to the heater 1216. In otherembodiments, the at least one temperature sensor 1220 can include onetemperature sensor or more than two temperature sensors.

Referring back to FIG. 11C, the first and second dry thawing chambers1202 a, 1202 b contain first and second opposing chamber frames 1222,1224, respectively, in which the power supply 1226 is positionedtherebetween. As shown in FIG. 6C, the first and second chamber frames1222, 1224 each have a base or bottom portion 1228, 1230 and a topportion 1232, 1234. The first chamber frame 1222 has first and secondopposing sidewalls 1236, 1238, extending between its base or bottomportion 1228 and top portion 1232. The second chamber frame 1224 has athird sidewall 1240 and a fourth, opposing sidewall that is obscured inFIG. 11C, each extending between the base or bottom portion 1230 and topportion 1234. The first chamber frame 1222 has a third heating assembly1242 that is pivotally mounted to a support frame 1244. The supportframe 1244 is slidably mounted to a track 1246, which is shown in moredetail in FIGS. 13A and 13B. While not shown, the track 1246 is fixedlymounted to the base or bottom portion 1228 of the first chamber frame1222. As such, the support frame 1244 is configured to slidably moverelative to the first chamber frame 1222.

Further, while obscured in FIG. 11C, the second chamber frame 1224includes a fourth heating assembly, a second support frame, and a secondtrack that are structurally similar to the third heating assembly 1242,the first support frame 1244, and the first track 1246 and together in asimilar fashion. As such, for sake of simplicity, the followingdescription is with respect to the third heating assembly 1242, thefirst support frame 1244, and the first track 1246, the first door 1204and the first heating assembly 1208 coupled thereto. A person skilled inthe art will understand, however, that the following discussion is alsoapplicable to the fourth heating assembly, the second support frame, andthe second track.

As shown in FIG. 11C and in more detail in FIGS. 13A-13B, the thirdheating assembly 1242 includes a heater 1248 and a heating cushion 1250coupled thereto. While the heater 1248 can have a variety ofconfigurations, as shown, the heater 1248 is in the form of a heaterplate. At least one temperature sensor 1252 is coupled to an outersurface 1250 a of the heating cushion 1250, and therefore in thermalcommunication therewith. The illustrated at least one temperature sensor1252 is configured to measure the temperature of the heating cushion1250 during use. While the at least one temperature sensor 1252 can havea variety of configurations, in this illustrated embodiment, the atleast one temperature sensor 1252 includes two temperature sensors, athermistor, e.g., a NTC thermistor, and a thermocouple. In certainembodiments, one of the two temperature sensors can be in communicationwith the power supply 1226 that is configured to supply electrical powerto the heater 1248. In such instances, when the measured temperature ofthe heating cushion 1250 exceeds a predetermined threshold temperature,the one of the two temperature sensors can transmit a failsafe signal tothe power supply 1226 that is operative to cause the power supply 1226upon receipt to terminate delivery of power to the heater 1248. In otherembodiments, the at least one temperature sensor 1252 can include onetemperature sensor or more than two temperature sensors.

While the support frame 1244 can have a variety of configurations, asshown, the support frame 1244 includes a base 1244 a and two supportarms 1244 b, 1244 c extending therefrom. As shown, the support frame1244 is mounted to the first track 1246. While the support frame 1244 isbiased in a first direction towards a first end 1246 a of the firsttrack 1246, the support frame 1244 is configured to slide along thefirst track 1246. That is, the support frame 1244 can slide in a seconddirection towards the between the first and second ends 1246 a, 1246 bof the first track 1246 so as to allow the first chamber frame 1222 toaccommodate for different volumes of an enclosed biological substancethat is to be thawed. Further, the sliding of the support frame 1244 canalso allow for and maintain an effective thermal communication betweenthe enclosed biological substance disposed between the first and thirdheating assemblies 1208, 1242.

While the support frame 1244 is biased in a first direction towards thefirst end of the first track 1246, This sliding of the support frame1244 between the first and second ends 1246 a, 1246 b of the first track1246 can be accomplished in a variety of ways. For example, in thisillustrated embodiment, a first biasing element 1254 and a secondbiasing element, obscured in FIGS. 11C and 13A-13B, are coupled betweenthe base 1244 a of the support frame 1244 and the first end 1246 a ofthe first track 1246. In this illustrated embodiment, the first biasingelement 1254 and the second biasing element are structurally similar,and therefore for sake of simplicity, the following description is withrespect to the first biasing element 1254. A person skilled in the artwill understand, however, that the following discussion is alsoapplicable to the second biasing element.

While the first biasing element 1254 can have a variety ofconfigurations, as shown in FIGS. 13A and 13B, the first biasing element1254 is a bi-stable spring band that is wound about a drum 1256 that ishoused within and connected to the base 1244 a of the support frame1244. The bi-stable spring band 1254 has a first end 1254 a that iscoupled to the first end 1246 a of the first track 1246 and a second end(obscured in FIGS. 11C and 13A-13B) that is coupled to the drum 1256. Inthis way, the support frame 1244 can linearly slide along the firsttrack 1246 between its first and second ends 1246 a, 1246 b, and thusrelative to the first chamber frame 1222.

FIGS. 16A and 16B illustrate the linear translation of the support frame1244 relative to the first chamber frame 1222 during use. While theheating cushion 1650 in FIGS. 16A and 16B is different than the heatingcushion 1250 shown in FIGS. 11C and 13A-13B, a person skilled in the artwill appreciate that the linear sliding movement of the support frame1244 is the same. For purposes of simplicity only, certain componentsare not illustrated in FIGS. 16A and 16B.

In use, an enclosed biological substance (not shown) is inserted intothe first chamber frame 1222 between the first heating assembly 1208(not shown) and the third heating assembly 1632, which is similar to thethird heating assembly 1242 except for the structural configuration ofthe heating cushion 1650. As the chamber door 1204 is moved from an openconfiguration to a closed configuration, the support frame 1244 can movein a second direction (D2) that is opposite the first direction (D1) inwhich the support frame 1244 is biased via the bi-stable spring band1254. For example, the support frame 1244 can move in the seconddirection (D2) from a first position as shown in FIG. 16A to a secondposition in FIG. 16B or any other position therebetween. As such, theforce being applied to the support frame 1244, e.g., by the enclosedbiological substance, the first and third heating assemblies 1208, 1632,and the chamber door 1204, is sufficient to overcome the biasing forceof the bi-stable spring band 1254. This causes the bi-stable spring band1254 to partially unwind from the drum 1256, thereby allowing thesupport frame 1244 to move. As a result, the enclosed biologicalsubstance is compressed between the first and third heating assemblies1208, 1632. This compression can help increase the surface contact areabetween the enclosed biological substance and the first and thirdheating assemblies 1208, 1632, thereby increasing the heatingefficiency. In certain instances, depending on the volume of theenclosed biological substance, the insertion of the enclosed biologicalsubstance alone can cause the support frame 1244 to slide in the seconddirection (D2).

Further, during heating, as the enclosed biological substance thaws, theposition of the support frame 1244 can be adjusted. That is, duringheating, as the force being applied to the support frame 1244 changes,the support frame 1244 can retract towards its first position (FIG. 16A)via the partial rewinding of the bi-stable spring band 1254 about thedrum 1256. Once the enclosed biological substance is removed from thefirst chamber frame 1222, the support frame 1244 can return to its firstposition as shown in FIG. 16A.

Referring back to FIGS. 13A and 13B, the third heating assembly 1242 ismounted to a first surface 1258 a (e.g., front surface) of an agitatorplate 1258. The agitator plate 1258 is pivotally coupled to the supportframe 1244. While the agitator plate 1258 can be pivotally coupled tothe support frame 1244 using a variety of mechanisms, in thisillustrated embodiment, a first set of pivot mounts 1260 a, 1260 b ofthe agitator plate 1258 and a second set of pivot mounts 1262 a, 1262 bof the support frame 1244 are coupled together via pivot pins 1264,1266. As a result, this pivoting engagement defines a pivot axis (PA) inwhich the agitator plate 1258, and thus the third heating assembly, canpivot relative to the first chamber frame to agitate an enclosedbiological substance that is contact therewith.

The pivotal motion of the agitator plate 1258, and thus the thirdheating assembly 1242, can be effected by an agitation device. Forexample, as shown in FIGS. 13A and 13B, an agitation device 1268 iscoupled to the support frame 1244 and configured to selectively contactthe second surface 1258 b of the agitator plate 1258 to cause pivotalmovement thereof. In this illustrated embodiment, the agitation device1268 is coupled to a chassis 1270 that is mounted between the twosupport arms 1244 b, 1244 c of the support frame 1244.

As shown in FIG. 14, the agitation device 1268 includes a motor 1272 anda cam 1274. The motor 1272 includes a rotary motor shaft 1272 a that iscoupled to the cam 1274 such that, upon actuation, the motor 1272 cancause the cam 1274 to rotate. While the cam 1274 can have a variety ofconfigurations, in this illustrated embodiment, the cam 1274 is oblongshaped. As a result, during rotation, the cam 1274 pushes on the secondsurface 1258 b of the agitator plate 1258 to causes the agitator plate1258 to pivot about the pivot axis (PA). This pivotal motion alternatesapplication of a compressive force against an enclosed biologicalsubstance and agitates the enclosed biological substance, e.g., duringheating. As a result, substantially even heating throughout the enclosedbiological substance can be effected.

FIGS. 17A and 17B illustrate the pivotal motion of the agitator plate1258 relative to the first chamber frame 1222 during use. While theheating cushion 1750 in FIGS. 17A and 17B is different than the heatingcushion 1250 shown in FIGS. 11C and 13A-13B, a person skilled in the artwill appreciate that the pivotal motion of the agitator plate 1258 isthe same. For purposes of simplicity only, certain components are notillustrated in FIGS. 17A and 17B.

In use, an enclosed biological substance (not shown) is inserted intothe first chamber frame 1222 between the first heating assembly 1208(not shown) and the third heating assembly 1732, which is similar to thethird heating assembly 1242 except for the structural configuration ofthe heating cushion 1750. Once the motor 1272 is activated, the cam 1274can rotate and come into contact with the agitator plate 1258, therebycausing the agitator plate 1258 to pivot in a first direction, denotedby arrow D1, to a first pivotal position, as shown in FIG. 17A. Thiscauses the top end 1258 c of the agitator plate 1258 to move towards thesupport frame 1244 and the bottom end 1258 d of the agitator plate 1258to move away from the support frame 1244. Since the first heatingassembly 1208 is fixed in place when the chamber door 1204 is closed,pivotal motion of the agitator plate 1258 in the first direction D1urges the enclosed biological substance upwards towards the top portion1232 (not shown) of the first chamber frame 1222. In some instances,this pivotal motion can also urge fluid (not shown) within the heatingcushion 1750 of the third heating assembly 1732 towards a top end 1258 cof the agitator plate 1258. As further shown in FIG. 17B, the agitatorplate 1258 can pivot in a second direction, denoted by arrow D2, fromthe first pivotal position to a second pivotal position. Since the firstheating assembly 1208 (not shown) is fixed and the cam 1274 rotates awayfrom the agitator plate 1258, pivotal motion of the agitator plate 1258in the second direction D2 is effected by downward movement of theenclosed biological substance, and in some instances, also the heatingcushion fluid, under the force of gravity. As such, the pivotal motionof the agitator plate 1258 can agitate the enclosed biological substancepositioned between the first and third heating assemblies 1208, 1732.

Referring back to FIGS. 13A-13B, a mounting bracket 1276, which is shownin more detail in FIG. 15, having a first portion 1276 a and a secondportion 1276 b extending therefrom. The first portion 1276 a of themounting bracket 1276 is coupled to and extends between the two supportarms 1244 b. The second portion 1276 b includes a hooking mount 1278having at least one hook 1278 a that is configured to engage and mountan enclosed biological substance, e.g., an enclosed biological substancedisposed within a bag assembly, like bag assembly 600, within the firstchamber frame 1222 and between the first and third heating assemblies1208, 1242. Further, the second portion 1276 b includes a weight sensor1279 that is configured to measure a weight of an enclosed biologicalsubstance, e.g., an enclosed biological substance disposed within a bagassembly, like bag assembly 600, that is engaged to the mounting bracket1276.

Temperature Sensors

The one or more temperature sensors can adopt a variety ofconfigurations. In certain embodiments, as will be discussed in greaterdetail below, the temperature sensors can be contact temperaturesensors, such as a first contact temperature sensor 124, a secondcontact temperature sensor 126, a third contact temperature sensor 130,and a fourth contact temperature sensor 132, as shown in FIG. 19A, andnon-contact temperature sensors, such as a first non-contact sensor 138,as shown in FIGS. 19B-19D, and combinations thereof. In one aspect,contact temperature sensors 124, 126 can be integrated with, or securedto, the enclosed biological substance (e.g., via an inner or outersurface of an overwrap bag, discussed below) for measurement of thetemperature of the enclosed biological substance. As an example, one ormore contact temperature sensors 124, 126 can be positioned on an innersurface of the overwrap bag for contact with the enclosed biologicalsubstance. In another aspect, contact temperature sensors 130, 132 canbe integrated with, or secured to, heating cushions (e.g., an inner orouter surface) for measurement of the temperature of heating cushions.In a further aspect, non-contact temperature sensors 138 can bedistanced from a target (e.g., the enclosed biological substance, theoverwrap bag, the heating cushion, etc.) and configured to measuretemperature of at least one target. As an example, non-contacttemperature sensors can measure electromagnetic radiation emitted fromthe enclosed biological substance (e.g., infrared radiation, dash-dotarrows).

In certain embodiments, the temperature sensors can communicate with thecontroller via communication links that are wired and/or wireless. As anexample, one or more of the contact temperature sensors (e.g., contacttemperature sensors 124, 126, 130, 132 shown in FIGS. 19A and 19D) canbe in integrated with a radiofrequency identification (RFID) tag mountedto the overwrap bag and/or the heating cushion. Mounting can includebeing printed on a surface, adhered to a surface by an adhesive, and thelike. In further embodiments, respective temperature sensors can be asensor of a smart label, as discussed in International PatentApplication No. WO 2016/023034, filed Aug. 10, 2015, entitled “Smart BagUsed In Sensing Physiological And/Or Physical Parameters Of BagsContaining Biological Substance,” the entirety of which is herebyincorporated by reference. The RFID tag can be configured to wirelesslytransmit temperature measurements to a receiver in communication withthe controller. While not shown, embodiments of the non-contact sensorscan also be configured to communicate wirelessly with the controller.

In further embodiments, the dry thawing chamber can include at least onecontact temperature sensor (e.g., contact temperature sensors 124, 126,130, 132 shown in FIGS. 19A and 19D) and at least one non-contacttemperature sensor (e.g., non-contact temperature sensor 138 shown inFIGS. 19B and 19D). This configuration can improve the accuracy oftemperature measurements and provide redundancy. In one example, faultytemperature sensors can be identified. For instance, temperaturemeasurements of the enclosed biological substance acquired by thecontact temperature sensors and non-contact temperature sensors can becompared to one another. If a deviation is observed between thesemeasurements, the controller can annunciate an alarm (e.g., an audioand/or visual signal) for replacement of the faulty temperature sensor.The alarm can also include a signal transmitted to the controller thatis operative to cause the controller to cease to employ the faultytemperature sensor for control of dry thawing processes. Redundancy canbe further provided by having the controller employ a non-faultytemperature sensor in place of the faulty temperature sensor for controlof dry thawing processes. In this manner, faulty temperature sensors canbe identified and replaced, while avoiding use of inaccurate temperaturemeasurements for control of dry thawing processes.

Dry Thawing Systems

FIGS. 19A-19D illustrate exemplary embodiments of a dry thawing system100 a, 100 b, 100 c, 100 d for thawing biological substances. Eachillustrated dry thawing system 100 a, 100 b, 100 c, 100 d includes a drythawing chamber 102, a controller 104, and a user interface 106. The drythawing chamber 102 can include one or more heating assemblies 108, 110,each having a heater 112, 114 that is in thermal communication with aheating cushion 116, 118. One or more heating cushions 116, 118 can beconfigured to be positioned in contact with an overwrap bag 120surrounding an enclosed biological substance 122 to thereby heat thesubstance. The dry thawing chamber 102 can also include one or moretemperature sensors for monitoring temperature of the enclosedbiological substance 122, one or more temperature sensors for monitoringtemperature of the one or more heating cushions 116, 118, and anagitation device 128 in mechanical communication with the overwrap bag120 (e.g., via heating assembly 108). The controller 104 can be placedin communication with the one or more heating assemblies 108, 110 andthe one or more temperature sensors by wired communication links and/orwireless communication links and it can be configured to employ one ormore of the temperature measurements for control of a dry thawingprocess. In this illustrated embodiment, the one or more heatingassemblies 108, 110 are in communication with the controller 104 viawired communication links 134 a, 134 b.

The one or more temperature sensors can adopt a variety ofconfigurations. FIG. 19A illustrates a first configuration of the one ormore temperature sensors including one or more first temperature contactsensors 124, 126 and one or more second contact temperature sensors 130,132. In one aspect, one or more first contact temperature sensors 124,126 can be integrated with, or secured to, the overwrap bag 120 (e.g.,secured to an inner or outer surface of the overwrap bag 120) formeasurement of the temperature of the enclosed biological substance 122.As shown, respective ones of the one or more first contact temperaturesensors 124, 126 are positioned on opposed, inner surfaces of theoverwrap bag 120 for contact with the enclosed biological substance 122.However, in alternative embodiments, the location and number of the oneor more first contact temperature sensors 124, 126 can be varied. In oneaspect, each of the one or more first contact temperature sensors 124,126 can be positioned on outer surfaces of the overwrap bag 120. Inanother aspect, one of the one or more first contact temperature sensors124, 126 can be positioned on an inner surface of the overwrap bag 120and the other of the one or more first contact temperature sensors 124,126 can be positioned on an outer surface of the overwrap bag 120. In afurther aspect, the one or more first contact temperature sensors 124,126 can be positioned on the same side of the overwrap bag 120. In anadditional aspect, fewer (e.g., 1) or greater (e.g., three or more)first contact temperature sensors can be employed without limit.

As further shown in FIG. 19A, the one or more second contact temperaturesensors 130, 132 can be integrated with, or secured to, heating cushions116, 118 (e.g., an inner or outer surface) for measurement of thetemperature of thereof. As shown, respective ones of the one or moresecond contact temperature sensors 130, 132 are positioned on outersurfaces of each heating cushion 116, 118. However, in alternativeembodiments, the location and number of the one or more second contacttemperature sensors 130, 132 can be varied. In one aspect, each of theone or more second temperature sensors 130, 132 can be positioned oninner surfaces of their corresponding heating cushions 116, 118 forcontact with the overwrap bag 120, and thus the enclosed biologicalsubstance 122. In another aspect, one of the one or more second contacttemperature sensors 130, 132 can be positioned on an inner surface ofits corresponding heating cushion 116, 118 and the other of the one ormore second contact temperature sensors 130, 132 can be positioned on anouter surface of its corresponding heating cushion 116, 118. In afurther aspect, the one or more second contact temperature sensors 130,132 can be positioned on the same heating cushion, e.g., either heating116 or heating cushion 118. In a further aspect fewer (e.g., 1) orgreater (e.g., three or more) second contact temperature sensors can beemployed without limit. In another aspect, the one or more secondcontact temperature sensors can be distributed between the heatingcushions in any combination.

In further aspects, the dry thawing system can include one or morenon-contact temperature sensors. The non-contact temperature sensors canbe distanced from a target (e.g., the enclosed biological substance, theoverwrap bag, the heating cushion, etc.) and configured to measuretemperature of at least one target. As an example, non-contacttemperature sensors can measure electromagnetic radiation emitted fromthe enclosure (e.g., infrared radiation 140).

In certain embodiments, the one or more non-contact temperature sensorscan be employed in combination with one or more contact temperaturesensors, as shown in FIGS. 19B-19D. In some embodiments, as shown inFIG. 19B, the dry thawing system 100 b includes a non-contacttemperature sensor 138 employed in combination with the one or morefirst contact temperature sensors 126, 124. In other embodiments, asshown in FIG. 19C, the dry thawing system 100 c includes a non-contacttemperature sensor 138 employed in combination with the one or moresecond contact temperature sensors 130, 132. In yet other embodiments,as shown in FIG. 19D, the dry thawing system 100 d includes anon-contact temperature sensor 138 employed in combination with the oneor more first contact temperature sensors 124, 126 and the one or moresecond contact temperature sensors 130, 132. In further alternativeembodiments, not shown, the contact temperature sensors (e.g., one ormore first contact temperature sensors 124, 126, and/or one or moresecond contact temperature sensors 130, 132) can be omitted and one ormore non-contact temperature sensors can be employed for measuring thetemperature of the enclosed biological substance, the overwrap bag,and/or the heating cushion.

In certain embodiments, the contact temperature sensors (e.g., one ormore first contact temperature sensors 124, 126 as shown in FIGS. 19A,19B, and 19D, and one or more second contact temperature sensors 130,132 as shown in FIGS. 19A, 19C, and 19D) and the non-contact temperaturesensors (e.g., non-contact temperature sensor 138 shown in FIGS.19B-19D) can communicate with the controller 104 via communication linksthat are wired and/or wireless. For example, as illustrated in FIGS.19A, 19B, and 19D, the one or more first contact temperature sensors124, 126 are in communication with the controller 104 via wirelesscommunication links 136 a, 136 b; as illustrated in FIGS. 19A, 19C, and19D, the one or more second contact temperature sensors 130, 132 are incommunication with the controller 104 via wired communication links 135a, 135 b; and as illustrated in FIGS. 19B-19D, the non-contacttemperature sensor 138 is in communication with the controller 104 viawired communication links 141.

In some embodiments, one or more of the contact temperature sensors canbe in integrated with a radiofrequency identification (RFID) tag mountedto the overwrap bag and/or the heating cushion. Mounting can includebeing printed on a surface, adhered to a surface by an adhesive, and thelike. In further embodiments, respective temperature sensors can be asensor of a smart label, as discussed in International PatentApplication No. WO 2016/023034, filed Aug. 10, 2015, entitled “Smart BagUsed In Sensing Physiological And/Or Physical Parameters Of BagsContaining Biological Substance,” the entirety of which is herebyincorporated by reference. The RFID tag can be configured to wirelesslytransmit temperature measurements to a receiver in communication withthe controller. While not shown, embodiments of the non-contacttemperature sensors can also be configured to communicate wirelesslywith the controller.

Beneficially, use of two or more temperature sensors selected fromcontact temperature sensors or non-contact temperature sensors improvesthe accuracy of temperature measurements and provides redundancy. In oneexample, faulty temperature sensors can be identified. For instance,temperature measurements of the enclosed biological substance 122acquired by two different temperature sensors (e.g., a pair oftemperature sensors selected from T₁, T₂, and T′) can be compared to oneanother. If a deviation is observed between these measurements, thecontroller 104 can annunciate an alarm (e.g., an audio and/or visualsignal) for replacement of the faulty temperature sensor. The alarm canalso include a signal transmitted to the controller 104 that isoperative to cause the controller 104 to cease to employ the faultytemperature sensor for control of dry thawing processes. Redundancy canbe further provided by having the controller 104 employ a non-faultytemperature sensor in place of the faulty temperature sensor for controlof dry thawing processes. In this manner, faulty temperature sensors canbe identified and replaced, while avoiding use of inaccurate temperaturemeasurements for control of dry thawing processes.

Embodiments of the dry thawing system can also be configured to providea failsafe functionality in which one or both of the heaters 112, 114stop generation of heat when the temperature measured by selected onesof the one or more of the heaters 112, 114 and the heating cushions 116,118 exceeds predetermined threshold temperatures. As shown in theembodiment of FIG. 1E, a dry thawing system 100 e can include one ormore first failsafe temperature sensors 144, 146 that are configured tomeasure the temperature of the one or more heaters 112, 114 during useand one or more second failsafe temperature sensors 148, 150 that areconfigured to measure the temperature of the one or more heatingcushions 116, 118 during use. The one or more first failsafe temperaturesensors 144, 146 and the one or more second failsafe temperature sensors148, 150 can be similar to the one or more first contact temperaturesensors 126, 124 and the one or more second contact temperature sensors130, 132 except that the one or more first failsafe temperature sensors144, 146 and the one or more second failsafe temperature sensors 148,150 are directly coupled to a power supply 107 that supplies electricalpower to the one or more heaters 112, 114. That is, in certainembodiments, the one or more first failsafe temperature sensors 144, 146and the one or more second failsafe temperature sensors 148, 150 are notin communication with the controller 104.

As such, the one or more first failsafe temperature sensors 144, 146 andthe one or more second failsafe temperature sensors 148, 150 cancommunicate with the power supply 107 via communication links 152 a, 152b, 154 a, 154 b that are wired and/or wireless. In this illustratedembodiment, the one or more first failsafe temperature sensors 144, 146and the one or more second failsafe temperature sensors 148, 150 are incommunication with the power supply 107 via wired communication links152 a, 152 b, 154 a, 154 b.

During use, the one or more first failsafe temperature sensors 144, 146and the one or more second failsafe temperature sensors 148, 150 can beconfigured to produce measurement signals (e.g., voltage, current, etc.)representative of their respective temperature measurements. Themeasurement signals can be compared to a threshold value representingthe corresponding predetermined threshold temperature. If the measuredtemperature represented by the measurement signal is greater than thepredetermined threshold temperature represented by the threshold value,a failsafe signal can be transmitted to the power supply 107.

The failsafe signal is operative to cause the power supply 107 toterminate delivery of electrical power independently to heaters 112,114. As an example, if a first failsafe signal is transmitted to thepower supply 107 in response to a temperature measurement made by eitherone of the first failsafe temperature sensor 144 or the second failsafetemperature sensor 148, delivery of electrical power can be terminatedto heater 112. Alternatively, if a second failsafe signal is transmittedto the power supply 107 in response to a temperature measurement made byeither one of the first failsafe temperature sensor 146 or the secondfailsafe temperature sensor 150, delivery of electrical power can beterminated to heater 114.

In certain embodiments, comparison of the measurement signal to thepredetermined threshold value can be performed by a logic circuit (notshown). The measurement signal represents the input to the logic circuitand the failsafe signal represents the corresponding output of the logiccircuit. In an embodiment, the logic circuit can integrated with each ofthe one or more first failsafe temperature sensors 144, 146 and the oneor more second failsafe temperature sensors 148, 150.

In an exemplary embodiment, the predetermined threshold temperaturevalue can be different for the heaters 112, 114 and the heating cushions116, 118. In one aspect, the predetermined threshold temperature for theheaters 112, 114 can be about 105° C. In another aspect, thepredetermined threshold temperature for the heating cushions 116, 118can be about 40° C. for embodiments of the one or more second failsafetemperature sensors 148, 150 in the form of a thermocouple and about 40°C. to about 60° C. for embodiments of the one or more second failsafetemperature sensors 148, 150 in the form of a thermistor (e.g., negativetemperature coefficient (NTC) thermistors and positive temperaturecoefficient (PTC) thermistors).

Thus, the one or more first failsafe temperature sensors 144, 146 andthe one or more second failsafe temperature sensors 148, 150 can preventdamage to the enclosed biological substance 122, overwrap bag 120,and/or other components of the dry thawing system 100 e. A personskilled in the art will appreciate that, while not shown, any of the drythawing systems 100 a, 100 b, 100 c, 100 d described above can alsoinclude one or more first failsafe temperature sensors 144, 146 and theone or more second failsafe temperature sensors 148, 150.

In use, the overwrap bag 120 containing the enclosed biologicalsubstance 122 is positioned in contact with the one or more heatingassemblies 108, 110 inside the dry thawing chamber 102. The one or moreheating cushions 116, 118 can be deformable to accommodate the shape andvolume of the overwrap bag 120 and the enclosed biological substance122. In this manner, contact between the overwrap bag 120 and the one ormore heating cushions 116, 118 can be ensured, promoting heat transferfrom the one or more heating cushion 116, 118 to the overwrap bag 120and the enclosed biological substance 122 contained therein.

The controller 104 can transmit first command signals to the firstheating assembly 108 and the second heating assembly 110 to cause thefirst heater 112 and the second heater 114, respectively, to generateheat, at least a portion of which is conducted through the first heatingcushion 116 and the second heating cushion 118, respectively, to theoverwrap bag 120, and consequently to the enclosed biological substance122. The temperature of a target can be measured by one or more contacttemperature sensors (e.g., first contact temperature sensors 124, 126and/or second contact temperature sensors 130, 132) and/or one or morenon-contact temperature sensors (e.g., non-contact temperature sensor138) and transmitted to the controller 104 via additional communicationlinks. The target can be at least one of the heating cushions 116, 118,the overwrap bag 120, and the enclosed biological substance 122.

It can be appreciated that, in certain embodiments, the temperature ofthe overwrap bag 120 can be approximately equal to the temperature ofthe enclosed biological substance 122. Accordingly, the temperature ofthe enclosed biological substance 122 can be referred to hereininterchangeably with the temperature of the overwrap bag 120.

The controller 104 can employ the measured temperatures as feedback forclosed-loop control of the heater 112, 114 of each of the one or moreheating assemblies 108, 110 and achievement of the predeterminedtemperature-time response. In certain embodiments, the controller 104can employ the temperature of the heating cushions 116, 118 of each ofthe one or more heating assemblies 108, 110 for closed-loop feedbackcontrol of the respective heaters 112, 114. In alternative embodiments,the controller 104 can employ the temperature of the enclosed biologicalsubstance 122 for closed-loop feedback control of the heaters 112, 114.Thus, regardless of the geometry or volume of the enclosed biologicalsubstance 122, heat applied for thawing the enclosed biologicalsubstance 122 can be controlled to avoid over-heating or under-heatingthe enclosed biological substance 122.

Substantially uniform heating can be achieved by use of the agitationdevice 128. The controller 104 can also transmit second command signalsto the agitation device 128 to agitate the enclosed biological substance122. As discussed in greater detail below, the agitation device 128 caninclude a motor configured to drive a rotating cam. The cam can bepositioned for contact with one of the heating assemblies, which ispivotably mounted within a frame. Reciprocating motion of the cam cancause one of the heating assemblies (e.g., first heating assembly 108shown in FIGS. 19A-19D) to reversibly pivot and apply compressive forcesagainst the overwrap bag 120 and enclosed biological substance 122. Inthis manner, the enclosed biological substance 122 can be urged to moveduring the thawing process, facilitating substantially even heatingthroughout the enclosed biological substance 122.

Substantially uniform heating can include its ordinary and customarymeaning understood by one of skill in the art. Substantially uniformheating can further include achieving a difference between a maximum andminimum temperature of the enclosed biological substance that is lessthan or equal to a predetermined temperature difference. Examples of thepredetermined temperature difference can be from the range of about 0.5°C. to about 2° C.

Heating Algorithm

Embodiments of the dry thawing system 100 a, 100 b, 100 c, 100 d, 800,900 can be configured to heat the enclosed biological substance 602 infour different stages: a pre-heating stage, an ice stage, a liquidstage, and a standby stage. Embodiments of flow diagrams illustratingeach of the stages are illustrated in FIGS. 20-23. Embodiments ofinterfaces generated by the user interface 822 during one or more ofthese stages are further presented in FIGS. 24-29. Exemplary temperatureset points and temperatures measured by the one or more temperaturesensors 124, 126, 130, 132, 138 during the different stages are furtherdiscussed in the context of FIG. 30.

FIG. 20 is a flow diagram illustrating one exemplary embodiment of amethod 2000, including operations 2002-2020, for pre-heating one or moredry thawing chambers 200, 804, 806, 904, 906. Pre-heating can beperformed prior to commencement of the ice stage. Pre-heating can allowthe selected dry thawing chamber(s) to be maintained at a predeterminedidle temperature when not in use, as long as the dry thawing 100 a, 100b, 100 c, 100 d, 800, 900 is powered on. Beneficially, the pre-heatingstage can reduce a total time required for thawing of the enclosedbiological substance 602.

Under circumstances where the dry heating system 100 a, 100 b, 100 c,100 d, 800, 900 is unpowered prior to the pre-heating stage, a power-upprocess can be performed prior to commencement of the pre-heating stage.Alternatively, under circumstances where the dry heating system 100 a,100 b, 100 c, 100 d, 800, 900 is powered prior to the pre-heating stage,the power-up process can be omitted. In further embodiments, thepre-heating stage can be omitted and the ice stage can begin followingthe power-up process.

As shown in FIG. 24, a user can employ an interface 2400 displayed bythe user interface 822 to initiate power up and pre-heating of one ormore selected dry thawing chambers 200, 804, 800, 904, 906. In operation2002 of FIG. 20, turning on power to the dry thawing system 100 a, 100b, 100 c, 100 d, 800, 900 can activate a built in self-test (BIT) of oneor more components of the dry thawing system 100 a, 100 b, 100 c, 100 d,800, 900. As an example, the BIT can include power on self-test (POST)of computing components, such as the controller 104, as well ascommunication links 134 a, 134 b, 135 a, 135 b, 136 a, 136 b, 141, 146a, 146 b and respective self-test routines of one or more of the heatingassemblies 108, 110, 400, 500, 1208, 1242, 1732, agitation devices 224,1268, temperature sensors 124, 126, 130, 132, 138, weight sensor 1279.In operation 2004, the controller 104 determines if any component(including itself) returns a signal indicating failure of its self-test(BIT OK?). If any component returns a signal indicating failure of itsself-test, BIT OK is NO, the method 2000 moves to operation 2006 and anerror message is displayed by the user interface 822. If no componentreturns a signal indicating failure of its self-test, BIT OK is YES, themethod 2000 moves to operation 2010 to commence the pre-heat stage.

In operation 2010, an available dry thawing chamber 200, 804, 800, 904,906 is selected. As an example, FIG. 25 illustrates an interface 2500displayed by the user interface 822 allowing an operator to select oneor more of the dry thawing chambers 200, 804, 800, 904, 906 (e.g.,chamber A and/or chamber B) for pre-heating. After input of the selecteddry thawing chamber 200, 804, 800, 904, 906 is received, the method 2000moves to operation 2012.

In operation 2012, the controller 104 generates one or more commandsignals 2012 s operative to control power delivered to the one or moreheating assemblies 108, 110, 400, 500, 1208, 1242, 1732 in thermalcommunication with the selected dry thawing chamber 200, 804, 800, 904,906 (e.g., the chamber frame 202, 1222, 1224) to effect the temperatureof respective heating cushions 116, 118, 1250, 1650, 1750 of the one ormore heating assemblies 108, 110, 400, 500, 1208, 1242, 1732. As anexample, the controller 104 is configured to perform closed-loop controlof the heating cushion temperature. In one aspect, the controller 104receives control parameters including a measured cushion temperatureT_(c) for at least one of the heating cushions 116, 118, 1250, 1650,1750 (e.g., from the one or more temperature sensors 124, 126, 130, 132,138), a pre-heating temperature set point temperature T_(ph), andpre-heating settings PID_(ph) (proportional-integral-derivative).

In order to generate the command signals 2012 s, the controller 104determines if there is a difference between each received measuredcushion temperature T_(c) and the pre-heating set point temperatureT_(ph) (T_(c)=T_(ph)?). If the controller 104 determines that there is adifference between the measured cushion temperature T_(c) and thepre-heating set point temperature T_(ph) (T_(c)=T_(ph) is NO), acorrection is calculated based upon this difference and PID_(ph). Thecorrection is transmitted from the controller 104 to respective ones ofthe heating assemblies 108, 110, 400, 500, 1208, 1242, 1732 as thecommand signal(s) 2012 s and the method 2100 returns to operation 2010.In operation 2010, the one or more heating assemblies 108, 110, 400,500, 1208, 1242, 1732 generate heat in response to receipt of thecommand signal(s) 2012 s. Subsequently, the method 2000 moves tooperation 2012 to again determine if there is a difference between eachmeasured cushion temperature T_(c) and the pre-heating set pointtemperature T_(ph). The operations 2010 and 2012 are repeated insequence until the measured cushion temperature T_(c) is about equal tothe pre-heating set point temperature T_(ph) (T_(c)=T_(ph) is YES).Subsequently, the method 2100 can move to operation 2014.

The pre-heating parameters T_(ph) and the PID_(ph) can be independentlyreceived by the controller 104 in in a variety of ways. In one aspect,these pre-heating parameters can be input by the operator via the userinterface 822. In another aspect, these pre-heating parameters can beretrieved from a memory. In a further aspect, these pre-heatingparameters can be hard-coded. In an embodiment, pre-heating set pointtemperature T_(ph) can range from about 35° C. to about 40° C. PID_(ph).In further alternative embodiments, at least one of the pre-heating setpoint temperature T_(ph) and PID_(ph) can be manually adjusted inreal-time by the operator during the pre-heating stage.

FIG. 30 illustrates one exemplary embodiment of the measured cushiontemperature T_(c) (dot-dash-dot line) and power P delivered to the oneor more heating cushions 116, 118, 1250, 1650, 1750 (dot-dot-dash line)with time during the pre-heating stage. Discussed above, the pre-heatingstage commences in operation 2010. Assuming that the pre-heating stagefollows the self-test operation preformed in method 2000, the measuredheating cushion temperature is about equal to room temperature T_(RT).That is, no heat is output by the one or more heating assemblies 108,110, 400, 500, 1208, 1242, 1732 and the heating power P is zero. Asshown, room temperature T_(RT) is less than the pre-heating set pointtemperature T_(ph). Thus, T_(c)=T_(ph) is NO and the controller 104transmits command signal(s) 2012 s operative to cause the heating powerP to increase and the one or more heating assemblies 108, 110, 400, 500,1208, 1242, 1732 generate heat. As shown, the heating power P can risefrom zero to a constant value. In response to the heat generation, themeasured cushion temperature T_(c) rises. Once the measured cushiontemperature T_(c) reaches the pre-heating set point temperature T_(ph),T_(c)=T_(ph) is YES, and the controller 104 further generates commandsignal(s) operative to maintain the cushion temperature T_(c) aboutequal to the pre-heating set point temperature T_(ph). As shown, theheating power can remain constant during the pre-heating stage. However,in alternative embodiments, the heating power can increase or decreaseas commanded by the controller 104 to achieve the pre-heating set pointtemperature T_(ph).

In operation 2014, the enclosed biological substance 602 is receivedwithin the selected dry thawing chamber 200. As an example, the chamberdoor 302, 809, 811, 909, 911, 1204 is opened to allow placement of theenclosed biological substance 602 within the chamber frame 202, 1222,1224. In certain embodiments, the enclosed biological substance 602 canbe within the overwrap bag 120, 606, 1000, 1100 and the overwrap bag120, 606, 1000, 1100 can be placed within the chamber frame 202, 1222,1224.

As shown in FIG. 26, the user interface 822 can be configured to displayan interface 2600 configured to allow input of selected informationregarding the enclosed biological substance 602. Alternatively oradditionally, an operator can employ the input device 824 (e.g., abarcode reader configured to read a barcode on the enclosed biologicalsubstance 122, 602, an RFID reader configured to receive informationstored by the RFID tag 1001, etc.) to automatically enter thisinformation. Examples of information regarding the enclosed biologicalsubstance 122, 602 can include information according to the ISBT 128standard. Examples include donation identification, product code, andclassification of the enclosed biological substance 122, 602 under theABO and/or RhD blood group system (ABO/RhD). The donation identificationcan be a unique identifier for the enclosed biological substance 122,602. The product code can specify physical parameters of the enclosedbiological substance 122, 602, such as volume. Further information caninclude an operator name and an expiration date/time.

In operation 2016, the controller 104 determines whether the chamberdoor 302, 809, 811, 909, 911, 1204 is closed (Door Closed?). In certainembodiments, the chamber door 302, 809, 811, 909, 911, 1204 can be incommunication with a door sensor (not shown) configured to output asignal in response to opening and closing of the chamber door 302, 809,811, 909, 911, 1204. Examples of the sensor can include mechanicalsensors (e.g., buttons), electromagnetic sensors (e.g., proximitysensors), and the like. The controller 104 can be in signalcommunication with the door sensor. Upon receipt of an open door signal,the controller 104 can command the user interface 822 to provide anannunciation (e.g., a sound, visual cue, prompt, etc.) to remind theoperator to confirm that the chamber door 302, 809, 811, 909, 911, 1204is closed. Alternatively, the controller 104 can refrain from displayingsuch a prompt under circumstances where a closed door signal is receivedwithin a predetermined time after receipt of the open door signal.

An affirmative input by the operator to the annunciation and/orsubsequent receipt of the closed door signal can be interpreted by thecontroller 104 as Door Closed=YES. A negative input or the absence ofinput to the annunciation can be interpreted by the controller 104 asDoor Closed=NO. Once the controller 104 determines that Door Closed=YES,the method 2000 moves to operation 2020.

In operation 2020, the controller 104 receives a measurement of theweight W of the enclosed biological substance 122, 602 from the weightsensor 1279 or a memory. If the controller 104 determines W>0 is NO, themethod 2000 returns to the loading operation of operation 2014. If thecontroller 104 determines that W>0 is YES, the method 2000 moves tooperation 2102 of method 2100.

Beneficially, the sequence of operations 2014-2020 confirms that anenclosed biological substance 122, 602 is received within the chamberframe 202, 1222, 1224 and that the chamber door 302, 809, 811, 909, 911,1204 is closed. In one aspect, if no enclosed biological substance 122,602 is present within the chamber frame 202, there is no purpose toexiting the pre-heating stage (moving to operation 2102 of method 2100).In another aspect, if the chamber door 302, 809, 811, 909, 911, 1204 isnot closed, significant heat may escape from the dry thawing system 100a, 100 b, 100 c, 100 d, 800, 900, inhibiting the achievement ofsubstantially uniform heating of the enclosed biological substance 122,602 and the pre-heating set point temperature T_(ph).

FIG. 21 is a flow diagram illustrating one exemplary embodiment of amethod 2100, including operations 2102-2124, for determining heatingparameters for the enclosed biological substance 122, 602 during the icestage based upon measured weight. As discussed above, embodiments of thedry thawing system 100 a, 100 b, 100 c, 100 d, 800, 900 can beconfigured to receive enclosed biological substances 122, 602 havingdifferent volume. It can be appreciated that, if the same heatingparameters are employed for significantly different volumes of theenclosed biological substance 122, 602, the amount of time required tocomplete the thawing process (e.g., the ice stage and the liquid stage)can vary significantly. Thus, it can be beneficial to employ differentheating parameters based upon the weight of the enclosed biologicalsubstance 122, 602. Examples of the heating parameters can include afirst cushion set point temperature T_(ci,1) within the ice stage, PIDsettings within the ice stage, and a transition set point temperatureT_(i) between the ice stage and the liquid stage. In this context, theindex i ranges from 1 to 4, representing four predefined weight ranges.However, alternative embodiments of the method can include greater orfewer weight ranges and the endpoints of the ranges can be varied asnecessary. For example, the weights can be selected between any twodesired endpoints (e.g., between about 0 g and about 500 g).

In operation 2102, the controller 104 determines if the weight W of theenclosed biological substance 122, 602 is greater than about apredetermined first weight W₁ and less than or equal to about apredetermined second weight W₂ (W₁<W≤W₂ ?). If W₁<W≤W₂ is YES, themethod 2100 moves to operation 2104, where the heating parametersT_(ci,1)=T_(c1,1), T_(i)=T₁, and PID_(i)=PID₁ are retrieved from memoryby the controller 104. If W₁<W≤W₂ is NO, the method 2100 moves tooperation 2106.

In operation 2106, the controller 104 determines if the weight W of theenclosed biological substance 122, 602 is greater than about thepredetermined second weight W₂ and less than or equal to about apredetermined third weight W₃ (W₂<W≤W₃ ?). If W₂<W≤W₃ is YES, the method2100 moves to operation 2110, where the heating parametersT_(ci,1)=T_(c2,i), T_(i)=T₂, and PID_(i)=PID₂ are retrieved from memoryby the controller 104. If W₂<W≤W₃ is NO, the method 2100 moves tooperation 2112.

In operation 2112, the controller 104 determines if the weight W of theenclosed biological substance 122, 602 is greater than the thirdpredetermined weight W₃ and less than or equal to about a predeterminedfourth weight W₄ (W₃<W≤W₄ ?). If W₃<W≤W₄ is YES, the method 2100 movesto operation 2114, where the heating parameters T_(ci,1)=T_(c3,1),T_(i)=T₃, and PID_(i)=PID₃ are retrieved from memory by the controller104. If W₃<W≤W₄ is NO, the method 2100 moves to operation 2116.

In operation 2116, the controller 104 determines if the weight W of theenclosed biological substance 122, 602 is greater than the fourthpredetermined weight W₄ and less than or equal to about a predeterminedfifth weight W₅ (W₄<W≤W₅ ?). If W₄<W≤W₅ is YES, the method 2100 moves tooperation 2120, where the heating parameters T_(ci,1)=T_(c4,1),T_(i)=T₄, and PID_(i)=PID₄ are retrieved from memory by the controller104. If W₄<W≤W₅ is NO, the method 2100 moves to operation 2122.

In operation 2122, the user interface 822 displays a warning. Display ofthe warning in operation 2122 can reflect an enclosed biologicalsubstance 122, 602 having a weight that does not fall within the rangesoutlined above. Following display of the warning in operation 2122, themethod 2100 can move to operation 2124, where the user interface 822displays the measured weight W of the enclosed biological substance 122,602 and requests operator input of the parameters T_(ci,1), T_(i), andPID_(i).

Exemplary embodiments of weight ranges are outlined in Table 1.

TABLE 1 Weight ranges Index, i Weight range 1 100 g < W ≤ 200 g 2 200 g< W ≤ 300 g 3 300 g < W ≤ 400 g 4 400 g < W ≤ 500 g

FIG. 22 is a flow diagram illustrating one exemplary embodiment of amethod 2200, including operations 2202-2216 for heating the enclosedbiological substance 122, 602 during the ice stage and liquid stage. Theice stage commences in operation 2202 and ends after completion ofoperation 2210, while the liquid stage commences in operation 2212 andends after completion of operation 2214. In general, the ice stagerepresents a condition of the enclosed biological substance 122, 602 inwhich a predetermined fraction of the enclosed biological substance 122,602 is solid (e.g., frozen). The liquid stage represents a condition ofthe enclosed biological substance 122, 602 in which a predeterminedfraction of the enclosed biological substance 122, 602 is liquid (e.g.,thawed).

In operation 2202, the controller 104 obtains the ice stage parametersT_(ci,1), T_(i), and PID_(i). As an example, Table 1 can be a lookuptable stored in memory and the ice stage parameters can be determined bythe controller 104 from this lookup table based upon the weight of theenclosed biological substance 122, 602.

In operation 2204, the controller 104 generates one or more commandsignals 2204 s operative to control power delivered to the one or moreheating assemblies 108, 110, 400, 500, 1208, 1242, 1732 to effect thetemperature of respective heating cushions 116, 118, 1250, 1650, 1750.As discussed above, the controller 104 is configured to performclosed-loop control of the heating cushion temperature.

In order to generate the command signals 2204 s, the controller 104determines if there is a difference between each measured cushiontemperature T_(c) and the first cushion set point temperature T_(ci,1)(T_(c)=T_(ci,1)?). As illustrated in Table 1, the first cushion setpoint temperature T_(ci,1) can range from about 37° C. to about 42° C.,based upon the weight W of the enclosed biological substance 122, 602.If the controller 104 determines that there is a difference between themeasured cushion temperature T_(c) and the first cushion set pointtemperature T_(ci,1) (T_(c)=T_(ci,1) is NO), a correction is calculatedbased upon this difference and PID_(i). The correction is transmittedfrom the controller 104 to respective ones of the heating assemblies108, 110, 400, 500, 1208, 1242, 1732 as the command signals 2204 s andthe method 2200 returns to operation 2202. In operation 2202, the one ormore heating assemblies 108, 110, 400, 500, 1208, 1242, 1732 generateheat in response to receipt of the command signal(s) 2204 s.Subsequently, the method 2200 moves to operation 2204 to again determineif there is a difference between each measured cushion temperature T_(c)and the first cushion set point temperature T_(ci,1). The operations2202 and 2204 are repeated in sequence until the measured cushiontemperature T_(c) is about equal to the first cushion set pointtemperature T_(ci,1) (T_(c)=T_(ci,1) is YES). Subsequently, the method2200 can move to operation 2206.

In operation 2206, the controller 104 determines whether the measuredtemperature T_(b) of the enclosed biological substance 122, 602 is equalto the transition set point temperature T_(i) (T_(b)=T_(i)?). In anembodiment, the transition set point temperature T_(i) can be atemperature above 0° C. at which most or all of the enclosed biologicalsubstance 122, 602 is melted into liquid. As illustrated in Table 1, thetransition set point temperature T_(i) can range from about 5° C. toabout 8° C. If T_(b)=T_(i) is NO in operation 2206, the method 2200returns to operation 2202. Alternatively, when T_(b)=T_(i) is YES inoperation 2206, the method 2200 moves to operation 2210, which ends theice stage and begins the liquid stage.

FIG. 30 illustrates one exemplary embodiment of the measured cushiontemperature T_(c) (dot-dash-dot line), the measured temperature T_(b),of the enclosed biological substance 122, 602 and power P delivered tothe one or more heating cushions 116, 118, 1250, 1650, 1750(dot-dot-dash line) as a function of time during the ice stage. Assumingthat the ice stage follows the pre-heating stage, at thawing time t=0,the measured cushion temperature T_(c) is about the pre-heating setpoint temperature T_(ph) and the measured temperature T_(b) of theenclosed biological substance 122, 602 is at an initial temperatureT_(o). The initial temperature T_(o) can be a temperature at which theenclosed biological substance 122, 602 is stored in its frozen state.

When transitioning from the pre-heating stage to the ice stage, the setpoint temperature for the heating cushion changes from the pre-heatingset point temperature T_(ph) to the first cushion set point temperatureT_(ci,1). As shown in FIG. 30, the first cushion set point temperatureT_(ci,1) is greater than the pre-heating set point temperature T_(ph).Thus, T_(c)=T_(ci,1) is NO in operation 2204 and the controller 104transmits command signal(s) 2204 s operative to cause the heating powerP to increase and the one or more heating assemblies 108, 110, 400, 500,1208, 1242, 1732 generate more heat. As shown, the heating power P canrise from the pre-heating stage power P_(ph) at thawing time t=0 to anice stage power level Pi.

In response to the increased heat generation during the ice stage, themeasured cushion temperature T_(c) rises. Once the measured cushiontemperature T_(c) reaches the first cushion set point temperatureT_(ci,1) (T_(c)=T_(ci,1) is YES in operation 2204), the controller 104further generates command signal(s) operative to maintain the cushiontemperature T_(c) about equal to the first cushion set point temperatureT_(ci,1). As shown, the heating power can remain about constant duringthe ice stage. However, in alternative embodiments, the heating power Pcan increase or decrease as commanded by the controller to achieve thefirst cushion set point temperature T_(ci,1).

Concurrently, the measured temperature T_(b) of the enclosed biologicalsubstance 122, 602 initially rises from T_(o) at thawing time t=0. Withincreasing time, the measured temperature T_(b) of the enclosedbiological substance 122, 602 increases until it reaches its meltingpoint. Subsequently, the heat generated by the one or more heatingassemblies 108, 110, 400, 500, 1208, 1242, 1732 is employed for melting,that is, a solid to liquid phase transition. While this phase transitionoccurs, the measured temperature T_(b) of the enclosed biologicalsubstance 122, 602 remains approximately constant. Once at least aportion of the enclosed biological substance 122, 602 becomes liquid,the measured temperature T_(b) of the enclosed biological substance 122,602 begins to increase again. The ice stage continues until the measuredtemperature T_(b) of the enclosed biological substance 122, 602 is aboutequal to the transition set point temperature T_(i) (T_(b)=T_(i) is YESin operation 2206).

The liquid stage begins in operation 2210 of method 2200. In operation2210, the controller 104 obtains the following liquid stage parameters:a second cushion set point temperature T_(c,L), a final set pointtemperature T_(f), and liquid stage PID settings PID_(L). The liquidstage parameters T_(c,L), T_(f), and PID_(L) can be independentlyreceived by the controller 104 in a variety of ways. In one aspect,these parameters can be input by the operator via the user interface822. In another aspect, these liquid stage parameters can be retrievedfrom a memory. In a further aspect, these liquid stage parameters can behard-coded. In certain embodiments, T_(c,L) can be selected from about35° C. to about 36° C. (e.g., about 36° C.).

In operation 2212, the controller 104 generates one or more commandsignals 2212 s operative to control power delivered to the one or moreheating assemblies 108, 110, 400, 500, 1208, 1242, 1732 to effect thetemperature of respective heating cushions 116, 118, 1250, 1650, 1750.As discussed above, the controller 104 is configured to performclosed-loop control of the heating cushion temperature.

In order to generate the command signals 2212 s, the controller 104determines if there is a difference between each measured cushiontemperature T_(c) and the second cushion set point temperature T_(c,L)(T_(c)=T_(c,L) ?). If the controller 104 determines that there is adifference between the measured cushion temperature T_(c) and the secondcushion set point temperature T_(c,L) (T_(c)=T_(c,L) is NO), acorrection is calculated based upon this difference and PID_(L). Thecorrection is transmitted from the controller 104 to respective ones ofthe heating assemblies 108, 110, 400, 500, 1208, 1242, 1732 as thecommand signals 2212 s and the method 2200 returns to operation 2202. Inoperation 2210, the one or more heating assemblies 108, 110, 400, 500,1208, 1242, 1732 generate heat in response to receipt of the commandsignal(s) 2212 s. Subsequently, the method 2200 moves to operation 2012to again determine if there is a difference between each measuredcushion temperature T_(c) and the first cushion set point temperatureT_(c,L). The operations 2210 and 2212 are repeated in sequence until themeasured cushion temperature T_(c) is about equal to the second cushionset point temperature T_(c,L) (T_(c)=T_(c,L) is YES). Subsequently, themethod 2200 can move to operation 2214.

In operation 2214, the controller 104 determines whether the measuredtemperature T_(b) of the enclosed biological substance 122, 602 is equalto the predetermined final set point temperature T_(f) (T_(b)=T_(f) ?).The final set point temperature T_(f) can represent a target temperaturefor the liquid stage. That is, a temperature sufficiently high to ensurethat all of the enclosed biological substance 122, 602 is thawed (e.g.,in the liquid phase) but not so high that the enclosed biologicalsubstance 122, 602 is thermally damaged. If T_(b)=T_(f) is NO inoperation 2214, the method 2200 returns to operation 2210, where thecontroller 104 continues to command the one or more heating assemblies108, 110, 400, 500, 1208, 1242, 1732 to generate heat. If T_(b)=T_(f) isYES in operation 2214, the method 2200 moves to operation 2216, whichends the liquid stage and begins the standby stage.

In general, the final set point temperature T_(f) can range from about0° C. to about 37° C. the exact value of the final set point temperatureT_(f) can be dependent upon the type of enclosed biological substanceand/or the weight of the enclosed biological substance. In an embodimentwhere the enclosed biological substance is a blood plasma, the final setpoint temperature T_(f) can range from about 30° C. to about 37° C.(e.g., about 33.5° C.). In an embodiment, the enclosed biologicalsubstance 122, 602 can be a blood component and the value of the finalset point temperature T_(f) can be based upon the blood componentaccording to standards set by regional, national, and/or internationalstandard bodies. In one embodiment, T_(f) can be determined pursuant tothe “Circular of Information for the Use of Human Blood and BloodComponents,” published by AABB, November 2017.

Referring again to FIG. 30, the measured temperature of the heatingcushion T_(c), the measured temperature T_(b) of the enclosed biologicalsubstance 122, 602, and power P delivered to the one or more heatingcushions 116, 118, 1250, 1650, 1750 (dot-dot-dash line) as a function oftime are also illustrated in the liquid stage. As shown, the liquidstage follows the ice stage. At thawing time t=t₁, the measured cushiontemperature T_(c) is about equal to the first cushion set pointtemperature T_(ci,1) and the measured temperature T_(b) of the enclosedbiological substance 122, 602 is about equal to the transition set pointtemperature T_(i).

When transitioning from the ice stage to the liquid stage, the set pointtemperature for the heating cushion changes from the first set pointtemperature T_(ci,1) to the second cushion set point temperatureT_(c,L). As shown in FIG. 30, the second cushion set point temperatureT_(c,L) is less than the first cushion set point temperature T_(ci,1).Thus, T_(c)=T_(c,L) is NO in operation 2212 and the controller 104transmits command signal(s) 2204 s operative to cause the heating powerP to decrease. That is, the one or more heating assemblies 108, 110,400, 500, 1208, 1242, 1732 generate less heat at the start of the liquidstage, as compared to the end of the ice stage, in order to decrease themeasured heating cushion temperature T_(c). As shown, the heating powerP can decrease from the ice stage power Pi at thawing time t=t₁.

In response to the reduction in heat generated by the heating assemblies108, 110, 400, 500, 1208, 1242, 1732, the measured cushion temperatureT_(c) decreases. Once the measured cushion temperature T_(c) reaches thesecond cushion set point temperature T_(c,L) (T_(c)=T_(c,L) is YES inoperation 2212), the controller 104 further generates command signal(s)operative to maintain the cushion temperature T_(c) about equal to thesecond cushion set point temperature T_(c,L). As shown, the heatingpower P can decrease throughout the duration of the liquid stage.However, in alternative embodiments, the heating power P can increase ordecrease as commanded by the controller 104 to achieve the secondcushion set point temperature T_(c,L).

Concurrently, the measured temperature T_(b) of the enclosed biologicalsubstance 122, 602 rises relatively rapidly from T_(i) at thawing timet=t₁. However, with increasing time, the slope of the temperature-timeresponse the measured temperature T_(b) of the enclosed biologicalsubstance 122, 602 decreases. The liquid stage continues until themeasured temperature T_(b) of the enclosed biological substance 122, 602is about equal to the final set point temperature T_(f) (T_(b)=T_(f) isYES in operation 2214).

With the conclusion of the liquid stage in operation 2214, the method2200 enters the standby stage when moving to operation 2216. Inoperation 2216, the controller 104 obtains the following standby stageparameters: a third cushion set point temperature T_(c,SB) and standbystage PID settings PID_(SB). The standby stage parameters T_(c,SB) andPID_(SB) can be independently received by the controller 104 in avariety of ways. In one aspect, the standby stage parameters can beinput by the operator via the user interface 822. In another aspect, thestandby stage parameters can be retrieved from a memory. In a furtheraspect, the standby stage parameters can be hard-coded. In certainembodiments, the third cushion set point temperature T_(c,SB) can beselected from about 35° C. to about 37° C. (e.g., about 35° C.)

During the standby stage of operation 2216, the controller 104 isfurther configured to maintain the temperature of the one or moreheating cushions 116, 118, 1250, 1650, 1750 to be about equal to thethird cushion set point temperature T_(c,SB). Similar to the discussionabove, in operation 2216, the controller 104 can generate standbycommand signals operative to control power delivered to the one or moreheating assemblies 108, 110, 400, 500, 1208, 1242, 1732 in order tomaintain the cushion temperature about equal to the standby set pointtemperature T_(c,SB). The standby command signals can be based upon thePID_(SB) and the difference between the measured cushion temperatureT_(c) and the fourth cushion set point temperature T_(c,SB).

When transitioning from the liquid stage, the set point temperature forthe heating cushion changes from the second set point temperatureT_(c,L) to the third cushion set point temperature T_(c,SB). However, asshown in FIG. 30, the third cushion set point temperature T_(c,SB) canbe about equal to the second cushion set point temperature T_(c,L).Furthermore, the heating power P can continue to decrease during thestandby stage. Concurrently, the measured temperature of the enclosedbiological substance 122, 602 can be about constant during the standbystage.

Embodiments of the controller 104 can also be configured to record theelapsed time of the ice stage, the liquid stage, and the standby stage.As discussed below, in certain embodiments, the controller 104 can alsobe configured to halt the thawing process during the method 2200 basedupon measurements of elapsed time.

As illustrated in FIG. 23, in operation 2302, the controller 104 zeros athawing time t maintained by a thawing timer after the pre-heating iscompleted and prior to the ice stage. In operation 2304, when the icestage commences at operation 2202, the thawing timer is started.

In operation 2306, while the thawing timer is running, the controller104 determines if the thawing time t exceeds a maximum thawing timet_(max) (t>t_(max) ?). In general, the maximum thawing time t_(max)represents a predetermined safe time duration for thawing of theenclosed biological substance 122, 602. Therefore, if t>t_(max) is YES,the method 2300 moves to operation 2310, entering a timeout condition.In the timeout condition, the controller 104 commands the one or moreheating assemblies 108, 110, 400, 500, 1208, 1242, 1732 to stopgenerating heat and generates a message for display by the userinterface 822 indicating the timeout condition and prompting theoperator to remove the enclosed biological substance 122, 602 from thedry thawing 100 a, 100 b, 100 c, 100 d, 800, 900 for disposal.Alternatively, if t>t_(max) is NO, the method 2300 moves to operation2312.

In operation 2312, the controller 104 determines when the liquid stagehas ended. Similar to operation 2214, the controller 104 determines theend of the liquid stage when the measured temperature T_(b) of theenclosed biological substance 122, 602 is equal to a the final set pointtemperature T_(f) (T_(b)=T_(f) ?). If T_(b)=T_(f) is NO, the method 2300returns to operation 2306. If T_(b)=T_(f) is YES, the method 2300 movesto operation 2214.

In operation 2314, the controller 104 records a first thawing time t₁elapsed for the ice stage, a second thawing time t₂ elapsed for theliquid stage, and a total thawing time t_(t) given by the sum of thefirst and second thawing times t₁, t₂. The thawing time t₁ is determinedfrom the start of operation 2202 to when T_(b)=T_(i) is YES in operation2206. The thawing time t₂ is determined from the ice stage time t₁ towhen T_(b)=T_(f) is YES in operation 2214. Subsequently, the method 2300moves to operation 2316.

In operations 2316-2324, the controller 104 monitors an amount ofstandby time t_(sb) elapsed during the standby stage. In general, it canbe desirable for the enclosed biological substance 122, 602 to beremoved from the dry thawing 100 a, 100 b, 100 c, 100 d, 800, 900shortly after the liquid stage is complete. Accordingly, the controller104 can alert the operator when the standby time t_(sb) exceeds apredetermined maximum standby time t_(sb), In operation 2316, thecontroller 104 zeros the standby timer t_(sb). In operation 2320, thecontroller 104 starts a standby timer to record the standby time t_(sb).

In operation 2322, the controller 104 determines whether the standbytime t_(sb) equals the maximum standby time t_(sb), max (t_(sb)=t_(sb),max ?). If t_(sb)=t_(sb, max) is NO, the method 2300 returns to 2322 andthe standby timer t_(sb) continues running. If t_(sb)=t_(sb, max) isYES, the method 2300 moves to operation 2324.

In operation 2324, the controller 104 generates a notification to alertthe operator that the maximum standby time t_(sb), max has been reached.The notification can include any audio and/or visual signal. Examplescan include audible alarms, lights, and messages displayed by the userinterface 822.

Subsequently, in operation 2326, the user interface 822 can display thecurrent temperature T_(b) of the enclosed biological substance 122, 602,the total thawing time t_(t) (t₁+t₂), and the standby time t_(sb). Thecontroller 104 can further return to the operation 2010 of method 2100to prepare the selected dry thawing chamber 200, 804, 800, 904, 906 forreceipt of another enclosed biological substance 122, 602.

FIG. 27 illustrates an embodiment of an interface 2700 displayed by theuser interface 822 during the ice stage and the liquid stage. As shown,the measured temperature t_(b) of the enclosed biological substance 122,602 (e.g., 20° C.) is displayed, as well as thawing time t elapsed fromcommencement of the ice stage at thawing time t=0. In certainembodiments, the first thawing time t₁ at which the transition betweenthe ice stage and the liquid stage occurs. An indicator light 2704 ofthe selected dry thawing chamber 200, 804, 800, 904, 906 (e.g., ChamberA) can also display a first color representing the status of theselected dry thawing chamber 200, 804, 800, 904, 906 as in use (e.g., anorange color). Alternatively or additionally, in further embodiments,the first color can be displayed by the user interface 822.

FIG. 28 illustrates an interface 2800 displayed by the user interface822 upon completion of the dry thawing process (e.g., operation 2326 ofmethod 2300). As shown, the measured temperature t_(b) of the enclosedbiological substance 122, 602 is displayed (e.g., 37° C.), as well asthe total time t_(t) elapsed in the dry thawing process and the standbytime t_(sb). The indicator light 2704 of the selected dry thawingchamber 200, 804, 800, 904, 906 can also display a second colorrepresenting the status of the selected dry thawing chamber 200, 804,800, 904, 906 as complete (e.g., a green color). Alternatively oradditionally, in further embodiments, the second color can be displayedby the user interface 822.

As illustrated in FIG. 29 the operator can select a “stop” option froman interface 2900 displayed by the user interface 822. The “stop” optioncan be selected at any time during the pre-heating stage, the ice stage,the liquid stage, or the standby stage. Selection of the “stop” optionduring any of the pre-heating stage, the ice stage, the liquid stage,and the standby stage aborts the thawing and/or heating process andcauses the controller 104 to cut power to the one or more heatingassemblies 108, 110, 400, 500, 1208, 1242, 1732. Selection of the “stop”option during the standby stage indicates that the dry thawing processhas been completed and the selected dry thawing chamber 200, 804, 800,904, 906 is available to receive another frozen biological substance.Following selection of the “stop” option during the standby stage, thecontroller 104 can return to the operation 2010 of method 2100 toprepare the selected dry thawing chamber 200, 804, 800, 904, 906 forreceipt of another enclosed biological substance 122, 602.

The terms and expressions which have been employed herein are used asterms of description and not of limitation, and there is no intention inthe use of such terms and expressions of excluding any equivalents ofthe features shown and described or portions thereof, but it isrecognized that various modifications are possible within the scope ofthe invention claimed. Thus, it should be understood that although thepresent invention has been specifically disclosed by preferredembodiments, exemplary embodiments and optional features, modificationand variation of the concepts herein disclosed may be resorted to bythose skilled in the art, and that such modifications and variations areconsidered to be within the scope of this invention as defined by theappended claims. The specific embodiments provided herein are examplesof useful embodiments of the present invention and it will be apparentto one skilled in the art that the present invention may be carried outusing a large number of variations of the devices, device components,methods steps set forth in the present description. As will be obviousto one of skill in the art, methods and devices useful for the presentmethods can include a large number of optional composition andprocessing elements and steps.

Values or ranges may be expressed herein as “about” and/or from/of“about” one particular value to another particular value. When suchvalues or ranges are expressed, other embodiments disclosed include thespecific value recited and/or from/of the one particular value toanother particular value. Similarly, when values are expressed asapproximations, by the use of antecedent “about,” it will be understoodthat here are a number of values disclosed therein, and that theparticular value forms another embodiment. It will be further understoodthat there are a number of values disclosed therein, and that each valueis also herein disclosed as “about” that particular value in addition tothe value itself. In embodiments, “about” can be used to mean, forexample, within 10% of the recited value, within 5% of the recited valueor within 2% of the recited value.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meanings as commonly understood by one of ordinary skillin the art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can be used inthe practice or testing of the present invention, the preferred methodsand materials are now described. Nothing herein is to be construed as anadmission that the invention is not entitled to antedate such disclosureby virtue of prior invention.

For purposes of describing and defining the present teachings, it isnoted that unless indicated otherwise, the term “substantially” isutilized herein to represent the inherent degree of uncertainty that maybe attributed to any quantitative comparison, value, measurement, orother representation. The term “substantially” is also utilized hereinto represent the degree by which a quantitative representation may varyfrom a stated reference without resulting in a change in the basicfunction of the subject matter at issue.

One skilled in the art will appreciate further features and advantagesof the invention based on the above-described embodiments. Accordingly,the invention is not to be limited by what has been particularly shownand described, except as indicated by the appended claims. Allpublications and references cited herein are expressly incorporatedherein by reference in their entirety. Any patent, publication, orinformation, in whole or in part, that is said to be incorporated byreference herein is incorporated herein only to the extent that theincorporated material does not conflict with existing definitions,statements, or other disclosure material set forth in this document. Assuch the disclosure as explicitly set forth herein supersedes anyconflicting material incorporated herein by reference.

1-13: (canceled) 14: A method for thawing a biological substance, themethod comprising: pivoting a first chamber door on a first side of ahousing from a closed position to an open position to provide access toa first cavity within the housing; positioning a first enclosedbiological substance in a frozen state into the first cavity in thehousing; pivoting the first chamber door to the closed position to causea first heating assembly mounted on the first chamber door to contactthe first enclosed biological substance; and activating the firstheating assembly to cause a first heater of the first heating assemblyto generate thermal energy to heat the first enclosed biologicalsubstance from the frozen state to a fluid state. 15: The method ofclaim 14, wherein, when the first chamber door is moved to the closedposition, the first enclosed biological substance is engaged between thefirst heating assembly on the first chamber door and a second heatingassembly disposed within the housing. 16: The method of claim 15,further comprising activating the second heating assembly to cause asecond heater of the second heating assembly to generate thermal energyto heat the first enclosed biological substance from the frozen state toa fluid state. 17: The method of claim 15, wherein the second heatingassembly is mounted on a first pivoting agitator plate, and wherein themethod further comprises activating a first agitation device to causethe first pivoting agitator plate to pivot and thereby agitate the firstenclosed biological substance. 18: The method of claim 14, furthercomprising monitoring a temperature of at least one of the first heatingassembly and the first enclosed biological substance. 19: The method ofclaim 14, further comprising pivoting a second chamber door on a secondside of a housing from a closed position to an open position to provideaccess to a second cavity within the housing; and positioning a secondenclosed biological substance in a frozen state into the second cavityin the housing. 20: The method of claim 19, further comprisingactivating a third heating assembly mounted on the second chamber doorto cause a third heater of the third heating assembly to generatethermal energy to heat the second enclosed biological substance from thefrozen state to a fluid state. 21: A method for thawing a biologicalsubstance, the method comprising: providing a dry thawing devicecomprising a housing, a first chamber frame disposed within the housing,wherein the first chamber frame comprises a first base extending from afirst end to a second end, a first chamber door pivotally mounted to thefirst end of the base and disposed at a first end of the housing, and afirst heating assembly mounted on an inner surface of the first chamberdoor; pivoting the first chamber door from a closed position to an openposition to provide access to a first cavity within the housing;positioning a first enclosed biological substance in a frozen state intothe first cavity; pivoting the first chamber door to the closed positionto cause the first heating assembly to contact the first enclosedbiological substance; and activating the first heating assembly to heatthe first enclosed biological substance from the frozen state to a fluidstate. 22: The method of claim 21, wherein the dry thawing devicefurther comprises a second heating assembly disposed within the housing,wherein the first and second heating assemblies define the first cavity.23: The method of claim 22, wherein the second heating assembly ismounted on an agitator plate disposed within the housing, and the methodfurther comprises pivoting the agitator plate about a pivot axis toagitate the first enclosed biological substance. 24: The method of claim23, wherein the agitator plate is pivotally mounted to a support that islinearly slidably mounted on the base of the first chamber frame. 25:The method of claim 21 further comprising measuring a temperature of atleast one of the first heating assembly and the first enclosedbiological substance within the cavity. 26: The method of claim 21further comprising measuring a weight of the first enclosed biologicalsubstance within the cavity. 27: The method of claim 21 furthercomprising placing the first enclosed biological substance into anoverwrap bag before positioning the first enclosed biological substanceinto the first cavity. 28: The method of claim 21, wherein the drythawing device further comprises: a second chamber frame disposed withinthe housing, wherein the second chamber frame comprises a second baseextending from a first end to a second end; and a second chamber doorpivotally mounted to the first end of the second base and disposed at asecond end of the housing opposite the first end. 29: The method ofclaim 22, wherein the dry thawing device further comprises: a secondchamber frame disposed within the housing, wherein the second chamberframe comprises a second base extending from a first end to a secondend; a second chamber door pivotally mounted to the first end of thesecond base and disposed at a second end of the housing opposite thefirst end; and a third heating assembly mounted on an inner surface ofthe second chamber door. 30: The method of claim 29 further comprising:pivoting the second chamber door from a closed position to an openposition to provide access to a second cavity within the housing;positioning a second enclosed biological substance in a frozen stateinto the second cavity in the housing; pivoting the second chamber doorto the closed position to cause the third heating assembly to contactthe second enclosed biological substance; and activating the thirdheating assembly to heat the second enclosed biological substance fromthe frozen state to a fluid state. 31: A method for thawing a biologicalsubstance, the method comprising: providing a dry thawing devicecomprising: a housing having opposed top and bottom sides, opposed frontand back sides extending between the top and bottom sides, and opposedleft and right sides extending between the top and bottom sides andbetween the front and back sides; and a first chamber door positioned onthe left side of the housing and comprising a first heating assemblymounted thereon; pivoting the first chamber door from a closed positionto an open position to provide access to a first cavity within thehousing; positioning a first enclosed biological substance in a frozenstate into the first cavity in the housing; pivoting the first chamberdoor to the closed position to cause the first heating assembly tocontact the first enclosed biological substance; and activating thefirst heating assembly to heat the first enclosed biological substancefrom the frozen state to a fluid state. 32: The method of claim 31,wherein the dry thawing device further comprises a second chamber doorpositioned on the right side of the housing, wherein the second chamberdoor comprises a second heating assembly mounted thereon, the methodfurther comprising: pivoting the second chamber door from a closedposition to an open position to provide access to a second cavity withinthe housing; positioning a second enclosed biological substance in afrozen state into the second cavity; pivoting the second chamber door tothe closed position to cause the second heating assembly to contact thesecond enclosed biological substance; and activating the second heatingassembly to heat the second enclosed biological substance from thefrozen state to a fluid state. 33: The method of claim 31, wherein thefirst and second chamber doors are mounted adjacent to the bottom sideof the housing such that an upper portion of each of the first andsecond chamber doors moves away from the top side of the housing whenpivoting each of the first and second chamber doors from the closedposition to the open position.